Matrix Metalloproteinase Expression
Published by Anonymous on 2007/9/24 (2790 reads)
1: J Cell Physiol. 2007 Apr;211(1):19-26.
Regulation of matrix metalloproteinase gene expression.
Yan C, Boyd DD.
MD Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA.
The metalloproteinases degrade extracellular matrix (ECM) components and activate growth factors, thereby contributing to physiological events (tissue remodeling in pregnancy, wound healing, angiogenesis) and pathological conditions (cancer, arthritis, periodontitis). The intent of this review is to bring together various studies on transcriptional and post-transcriptional control of metalloproteinase expression. Certainly, much information is known as to the cis-elements and corresponding trans-activators regulating expression of these genes. We discuss the fact that a number of the metalloproteinase promoters share common structural features and, therefore, not surprisingly are co-regulated in their expression to some extent. More recently, much effort has been devoted to understanding the role of chromatin in regulating gene expression. While this area has been understudied with respect to matrix metalloproteinase (MMP) regulation, the literature indicates a convincing role for both histone modifications and chromatin-remodeling motors in controlling expression of multiple metalloproteinases. In addition to transcriptional control, mRNA stability and protein translation also contribute to the metalloproteinase product amount. We discuss such studies and how various biological cues, including TGF-beta, regulate the levels of certain collagenases either solely through mRNA stabilization or by jointly targeting transcriptional and post-transcriptional mechanisms. We also discuss the current deficits in our knowledge, concerning tissue-specific expression and why despite elevated amounts/activity of trans-activators targeting MMP promoters in tumor cells, nevertheless, MMP expression is largely restricted to the stromal compartment. Finally, we argue for potential technologies to regulate MMP expression of utility in pathological conditions where these enzymes are aberrantly expressed. (c) 2006 Wiley-Liss, Inc.
Publication Types:
Research Support, N.I.H., Extramural
Review
PMID: 17167774 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: Curr Opin Rheumatol. 2006 Jul;18(4):364-8.
Matrix metalloproteinase expression in the spondyloarthropathies.
Zhu J, Yu DT.
Rheumatology Department, Chinese PLA General Hospital, Beijing, China.
PURPOSE OF REVIEW: Expression of matrix metalloproteinases and their tissue inhibitors has been an active area of investigation in rheumatoid arthritis and osteoarthritis. Only recently have investigators started to study these factors in spondyloarthropathy. The purpose of this review is to summarize these recent findings. RECENT FINDINGS: Multiple matrix metalloproteinases and their tissue inhibitors are expressed in the synovial fluid as well as serum samples of spondyloarthropathy patients. Their degrees of expression in the synovia correlate with parameters of arthritis activity such as cell infiltration. In the synovial fluids, the factor which is expressed in very high level is matrix metalloproteinase-3. Two separate cohorts demonstrate that serum levels of matrix metalloproteinase-3 correlate with disease activity in ankylosing spondylitis. Their usefulness appears to exceed those of erythrocyte sedimentation rate and C-reactive protein. Multiple studies also indicate that serum levels of matrix metalloproteinase-3 are suppressed when patients are treated with the anti-tumor necrosis factor-alpha antibody infliximab. SUMMARY: New biomarkers are in demand for spondyloarthropathy in deciding whether patients would benefit from treatment with tumor necrosis factoralpha blockers, monitoring response to treatment, or predicting potential of joint damage if untreated. Recent studies show that among the matrix metalloproteinase and their tissue inhibitors, serum MMP-3 is the one with potential usefulness.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 16763456 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: Front Biosci. 2006 May 1;11:1199-215.
Regulation of matrix metalloproteinase (MMP) gene expression by protein kinases.
Reuben PM, Cheung HS.
Research Service and Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Miami, Florida 33125, USA.
Matrix metalloproteinases (MMPs) are a family of structurally and functionally related zinc-containing endopeptidases that are capable of degrading almost all of the components of the extracellular matrix (ECM). Under physiological and pathological conditions, the MMPs play a significant role in the efficient tissue turnover and remodeling. Specific MMPs are responsible for the matrix degradation and remodeling. Maintenance of the equilibrium between deposition and degradation of the extracellular matrix is essential to the normal tissue development. Therefore, synthesis and breakdown of the MMPs are tightly controlled by protein kinases which mediate a host of other cellular processes. The MMPs are often induced by several agents and any uncontrolled expression of the MMPs can contribute to the pathogenesis of many human diseases. This review focuses on the regulation of the MMPs by the protein kinases at the level of gene expression and their signaling pathways.
Publication Types:
Review
PMID: 16368506 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Nippon Rinsho. 2005 Nov;63 Suppl 11:138-45.
[Helicobacter pylori induces matrix metalloproteinase expression]
[Article in Japanese]
Mori N.
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus.
Publication Types:
Review
PMID: 16363520 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Clin Orthop Relat Res. 2004 Oct;(427 Suppl):S129-37.
Novel inhibitors of matrix metalloproteinase gene expression as potential therapies for arthritis.
Mix KS, Sporn MB, Brinckerhoff CE, Eyre D, Schurman DJ.
Department of Biochemistry, Dartmouth Medical School, Lebanon, NH 03756, USA.
Matrix metalloproteinases are a family of endopeptidases that collectively degrade all components of the extracellular matrix at neutral pH. During the progression of arthritis, MMPs mediate the degradation of cartilage, which consists largely of Type II collagen fibrils and proteoglycans. The collagenases, a subgroup of MMPs, have the singular ability to cleave intact collagens and may provide a rate-limiting step in cartilage destruction. In arthritic lesions, collagenase-1 (matrix metalloproteinase-1) and collagenase-3 (matrix metalloproteinase-13) mediate the irreversible destruction of cartilage, suggesting that these enzymes are therapeutic targets. We describe the role of metalloproteinases in the destruction of connective tissues in arthritis and the treatment strategies that have been developed to block matrix metalloproteinases in an attempt to prevent this destruction. We also discuss novel compounds that may selectively inhibit these cartilage-degrading enzymes, providing opportunities to develop new therapeutic approaches.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 15480055 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
6: Q J Nucl Med. 2003 Sep;47(3):201-8.
Imaging matrix metalloproteinase expression in tumors.
Li WP, Anderson CJ.
Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
metastatic Matrix metalloproteinases (MMPs) are zinc-dependent secreted or transmembrane enzymes constituting a family of over 21 proteolytic members that are capable of selectively digesting a wide spectrum of both extracellular matrix (ECM) and nonmatrix proteins. MMPs play a critical role in tumor growth, angiogenesis, and metastatic processes. MMP inhibitors (MMPIs) have been extensively investigated as anti-tumor drugs, although the clinical trials thus far have been disappointing. In order to better understand the role of MMPs in cancer growth and metastasis, as well as improve the therapeutic efficacy of MMPIs, there is a need to develop new procedures to assess and/or monitor MMP activity in vivo. In addition to determining whether MMPs are present in tumors, it would be desirable to have an imaging agent that better probes other processes associated with MMP overproduction, including angiogenesis and the establishment of the growth of metastatic lesions in distant organ sites. In this paper we review the studies relating to the recent development of in vivo imaging of MMP expression. One of the purposes of this review is to discuss the current status of imaging MMP expression, which includes the types of tracers being developed and the types of imaging modalities available. Although imaging MMP expression is a relatively new area of research, the progress thus far is highly promising.
Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 12897711 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
7: Front Biosci. 2003 Jan 1;8:d78-86.
Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression.
Osteen KG, Igarashi TM, Bruner-Tran KL.
Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. Kevin.osteen@vanderbilt.edu
The endometrium is a unique adult tissue which, in the absence of pregnancy or disease, undergoes cyclic breakdown and regrowth approximately 400 times during a woman's reproductive life. The chances of reproductive success during each cycle depends on appropriate, cell-specific responses to steroids, including expression of matrix metalloproteinases (MMPs). Normal endometrial MMP regulation in response to either estrogen or progesterone requires additional, cell-specific interactions mediated by various growth factors and cytokines. During endometrial maturation, progesterone, retinoic acid and TGF-beta act cooperatively, providing a remarkable biological balance to regulate expression of MMPs in the highly steroid-sensitive endometrium. Exploring the regulatory actions of locally produced growth factors and cytokines on members of the MMP family and their inhibitors will allow a better understanding of the unique physiology of the human endometrium under the influence of progesterone.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 12456342 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
8: Methods Mol Med. 2003;74:349-56.
Matrix metalloproteinase expression in lung cancer.
Lim M, Jablons DM.
Thoracic Oncology Program, University of California San Francisco/Mount Zion Medical Center, San Francisco, CA, USA.
Publication Types:
Review
PMID: 12415707 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
9: Cardiovasc Res. 2002 Jun;54(3):495-8.
Comment on:
Cardiovasc Res. 2002 Jun;54(3):549-58.
Matrix metalloproteinase-9 expression after myocardial infarction: physiological or pathological?
Thompson MM, Squire IB.
Publication Types:
Comment
Editorial
Review
PMID: 12031694 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
10: Ann N Y Acad Sci. 2002 Mar;955:139-46; discussion 157-8, 396-406.
Paracrine mediators of endometrial matrix metalloproteinase expression: potential targets for progestin-based treatment of endometriosis.
Osteen KG, Bruner-Tran KL, Ong D, Eisenberg E.
Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University of Medicine, Nashville, Tennessee 37232, USA. kevin.osteen@mcmail.vanderbilt.edu
The endometrial lining of the human uterus is a highly specialized, steroid-sensitive tissue. Throughout the reproductive years, the endometrium undergoes dramatic cycles of growth, differentiation, and breakdown under the influence of ovarian steroids. In response to changes in steroid exposure throughout the menstrual cycle, the endometrium produces an array of bioactive growth factors and other cytokines that are critical components of paracrine communication. For example, cell-cell communication via paracrine factors directs the expression of matrix metalloproteinases (MMPs), enzymes that mediate tissue remodeling during the menstrual cycle. The disease endometriosis is thought to occur as a consequence of retrograde menstruation, and MMPs appear to contribute to the establishment and progression of ectopic endometrial growth in the peritoneal cavity. Although the risk for developing endometriosis is linked to a woman's steroid exposure, locally produced paracrine factors can modify steroid action on multiple gene targets, including the MMPs. Estrogen-associated growth factors as well as inflammatory cytokines are potent stimulators of MMP expression and may contribute to the ability of endometrial fragments to invade the peritoneal surface and establish ectopic sites of growth. In contrast, paracrine factors associated with progesterone action during early pregnancy inhibit MMP expression and prevent ectopic endometrial growth in an experimental model. For example, locally produced retinoic acid and transforming growth factor-beta (TGF-beta) act in concert with progesterone to suppress MMPs, while enhancing expression of MMP inhibitors (TIMPs) during endometrial differentiation. Targeting pregnancy-associated factors that inhibit endometrial-specific MMP expression and action may enhance the effectiveness of progestin-related treatments for endometriosis.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 11949943 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
11: Methods Mol Biol. 2001;151:121-48.
The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression.
Vincenti MP.
Department of Medicine and Biochemistry, Dartmouth Medical School, Hanover, NH, USA.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 11217296 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
12: Matrix Biol. 2000 Dec;19(7):623-9.
Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases.
Ye S.
Human Genetics Research Division, School of Medicine, University of Southampton, UK. shu.ye@soton.ac.uk
The matrix metalloproteinases (MMPs) can degrade a range of extracellular matrix proteins and have been implicated in connective tissue destruction and remodelling associated with cancer invasion and metastasis, cartilage destruction in arthritis, atherosclerotic plaque rupture, and the development of aneurysms. Recently, naturally occurring sequence variation has been detected in the promoter of a number of MMP genes. These genetic polymorphisms have been shown to have allele-specific effects on the transcriptional activities of MMP gene promoters, and to be associated with susceptibility to coronary heart disease, aneurysms and cancers. These findings indicate that variation in the MMP genes may contribute to inter-individual differences in susceptibility to these common, complex diseases, likely through effects on the balance between the synthesis and degradation of extracellular matrix proteins.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 11102751 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
13: Gynecol Obstet Invest. 1999;48 Suppl 1:2-13.
Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium.
Osteen KG, Keller NR, Feltus FA, Melner MH.
Women's Reproductive Health Research Center, Vanderbilt University School of Medicine, Nashville, Tenn. 37232, USA. kevin.osteen@mcmail.vanderbilt.edu
Endometrial expression of matrix metalloproteinase (MMP)-3, MMP-7 and MMP-11 occurs during menstrual breakdown and subsequent estrogen-mediated growth, but not during the secretory phase. These enzymes are suppressed by progesterone treatment. Paracrine factors, including transforming growth factor-beta (TGF-beta) and retinoic acid, are also critical for MMP regulation in the endometrium. In contrast, inflammatory cytokines such as interleukin-1alpha may block or interfere with steroid-mediated MMP regulation at ectopic sites of growth. Using in vitro models, our laboratory has investigated the complex interactions between progesterone and locally produced cytokines that may affect MMP expression during the development of endometriosis. Our results indicate that targeting the regulation of MMPs may represent an appropriate therapeutic strategy for the treatment of endometriosis. Copyrightz1999S. KargerAG,Basel
Publication Types:
Review
PMID: 10559659 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
14: FASEB J. 1999 May;13(8):781-92.
Regulation of matrix metalloproteinase expression in tumor invasion.
Westermarck J, Kähäri VM.
MediCity Research Laboratory, Department of Medical Biochemistry, University of Turku, Finland. jukwes@utu.fi
Degradation of basement membranes and stromal extracellular matrix (ECM) is crucial for invasion and metastasis of malignant cells. Degradation of ECM is initiated by proteinases secreted by different cell types participating in tumor cell invasion, and increased expression or activity of every known class of proteinases (metallo-, serine-, aspartic-, and cysteine) has been linked to malignancy and invasion of tumor cells. Studies performed over the last decade have revealed that matrix metalloproteinases (MMPs) play a crucial role in tumor invasion. Expression of MMP genes is transcriptionally regulated by a variety of extracellular factors including cytokines, growth factors, and cell contact to ECM. This review will summarize the current view on the role of MMPs in tumor growth, invasion, and survival, and focus on the role of mitogen-activated protein kinases and AP-1 and ETS transcription factors in the regulation of MMP gene expression during invasion process.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 10224222 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
15: Arch Dermatol Res. 1998 Jul;290 Suppl:S47-54.
Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers.
Saarialho-Kere UK.
Department of Dermatology, Helsinki University Central Hospital, Finland. ulpu.saarialho-kere@helsinki.fi
Controlled proteolysis is needed for cell migration, angiogenesis, and matrix remodeling during normal wound repair. Our objective has been to investigate how chronic leg ulcers differ from normally healing wounds (pinch graft donor sites) with respect to their metalloproteinase expression patterns. Using in situ hybridization and immunohistochemistry, we found that collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) were expressed in keratinocytes bordering both acute and chronic wounds. Unlike MMP-1, signal for collagenase-3 (MMP-13) was not detected in keratinocytes but exclusively in fibroblasts deep in the ulcer bed of chronic wounds, suggesting that while MMP-1 production is important for migration, MMP-13 plays a role in matrix remodeling. Tissue inhibitor of metalloproteinase (TIMP)-1 was not detected in the epidermis of any chronic wound sample while it was expressed in keratinocytes bordering normally healing wounds. TIMP-3 was abundantly expressed in stromal fibroblast- and macrophage-like cells surrounding vessels and sweat glands in both types of wounds. Our results suggest that there are no qualitative differences in the expression of MMPs-1, -3 and -10 in the epidermis of chronic vs normally healing wounds. However, the number of stromal cells expressing MMP-1 and MMP-3 was greater in chronic vs acute wounds, whereas MMP-10 was never detected in the dermis. TIMP-1 expression near the basement membrane in acute, but not in chronic, wounds suggests that the balance between MMPs and their inhibitors may be altered in poorly healing wounds. Analogous to chronic cutaneous wounds, MMP-1 and -3 are abundantly expressed in chronic small and large bowel ulcers, while the migrating surface epithelium is negative for TIMP-1 expression.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 9710383 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
16: Semin Reprod Endocrinol. 1996 Aug;14(3):247-55.
Steroid and growth factor regulation of matrix metalloproteinase expression and endometriosis.
Osteen KG, Bruner KL, Sharpe-Timms KL.
Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Publication Types:
Review
PMID: 8885055 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
17: Gene Expr. 1996;6(4):197-207.
Nuclear hormone receptors inhibit matrix metalloproteinase (MMP) gene expression through diverse mechanisms.
Schroen DJ, Brinckerhoff CE.
Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.
Agents like retinoids, thyroid hormone, glucocorticoids, progesterone, androgens, which bind to members of the nuclear receptor superfamily, inhibit the synthesis of matrix metalloproteinases (MMPs) in many cell types. These Zn2(+)- and Ca2(+)-dependent MMPs degrade components of the extracellular matrix (ECM), and precise regulation of their expression is crucial in many normal processes. However, inappropriate expression of MMPs contributes to a variety of invasive and erosive diseases, and inhibition of MMP synthesis provides an important mechanism for controlling such aberrant or dysregulated responses. Nuclear receptors control MMPs through a variety of seemingly redundant mechanisms. First, nuclear receptors act on the promoters of MMP genes to enhance or suppress trans-activation. Ironically, in a family of genes that exhibits substantial regulation by nuclear receptors, few consensus hormone responsive elements (HREs) have been deomonstrated in MMP promoters. Rather, inhibition of MMPs occurs primarily, but not exclusively, at AP-1 sites. Here, nuclear receptors form complexes on the DNA through interactions with AP-1 proteins, sequester Fos/Jun and/or decrease the mRNAs for these transcription factors. Second, nuclear receptors and their ligands can indirectly inhibit MMPs. For instance, both retinoids and glucocorticoids induce the transcription of TIMPs (tissue inhibitor of metalloproteinases), which complex with MMPs and inhibit enzymatic activity, and progesterone stimulates production of transforming growth factor-beta (TGF-beta), which in turn suppresses MMP-7 (matrilysin). Finally, nuclear receptors bind to coactivators, corepressors, and components of the general transcriptional apparatus, but the potential role of these interactions in MMP regulation remains to be determined. We conclude that nuclear receptors utilize multiple, apparently redundant, mechanisms to inhibit MMP gene expression, assuring precise control of ECM degradation under a variety of physiologic and pathologic conditions.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 9196075 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
18: Crit Rev Eukaryot Gene Expr. 1996;6(4):391-411.
Regulating expression of the gene for matrix metalloproteinase-1 (collagenase): mechanisms that control enzyme activity, transcription, and mRNA stability.
Vincenti MP, White LA, Schroen DJ, Benbow U, Brinckerhoff CE.
Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.
Matrix metalloproteinase-1 (MMP-1) is one of three collagenases that can degrade the interstitial collagens, types I, II, and III at neutral pH. As these collagens are the most abundant proteins in the body, collagenase plays a critical role in modeling and remodeling the extracellular matrix. Therefore, it is not surprising that MMP-1 gene expression can be regulated at multiple points. Procollagenase can be activated by mechanisms that generate an active enzyme with differing specific activities, and the active enzyme can be inhibited by complexing with either the tissue inhibitor of metalloproteinases (TIMPs) or alpha 2 macroglobulin. The activator protein-1 (AP-1) site in the collagenase promoter plays a prominent role in the transcriptional control of the collagenase gene. It is essential for basal transcription, and contributes to induction by phorbol esters, although other sites in the proximal promoter are essential. In contrast, transactivation by cytokines such as Interleukin-1 depends on sequences in more distal regions of the promoter. Posttranscriptional mechanisms also regulate gene expression, and several cytokines and growth factors increase the stability of the collagenase transcript. Finally, glucocorticoid hormones repress transcription of the collagenase gene by the interaction of glucocorticoid receptors with the AP-1 proteins, Fos and Jun. Retinoids also suppress transcription by mechanisms that involve down-regulation of fos and jun mRNA, sequestration of Fos and Jun proteins, and the formation of complexes of retinoic acid receptors (RAR/RXR heterodimers) and AP-1 proteins on the DNA. These multiple points of regulation assure precise control of collagenolytic activity in a variety of physiologic and pathologic conditions.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 8959374 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
19: Ann N Y Acad Sci. 1994 Sep 6;732:42-50.
Matrix metalloproteinase gene expression.
Matrisian LM.
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 7978826 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
20: Immun Infekt. 1993 Apr;21 Suppl 1:20-1.
[The matrix metalloproteinase gene family: structure, function, expression, and role in destructive joint disease]
[Article in German]
Conca W.
Abteilung Rheumatologie und Klinische Immunologie, Medizinische Universitätsklinik Freiburg.
The matrix metalloproteinases, i.e. collagenases, gelatinases and stromelysins, are members of a gene family. They are capable of degrading every component of the extracellular matrix. Tissue destruction observed in inflammatory joint disease is largely accounted for by the action of these enzymes. Among the most potent inducers of metalloproteinase expression are the inflammatory cytokines IL-1 and TNF-alpha. Studies of mechanisms of induction by these mediators at the transcriptional level have improved our understanding of the biological controls of metalloproteinase synthesis. Cytokine inhibitors might serve to inhibit or postpone the crippling consequences of metalloproteinase action.
Publication Types:
English Abstract
Review
PMID: 8344678 [PubMed - indexed for MEDLINE]
Regulation of matrix metalloproteinase gene expression.
Yan C, Boyd DD.
MD Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA.
The metalloproteinases degrade extracellular matrix (ECM) components and activate growth factors, thereby contributing to physiological events (tissue remodeling in pregnancy, wound healing, angiogenesis) and pathological conditions (cancer, arthritis, periodontitis). The intent of this review is to bring together various studies on transcriptional and post-transcriptional control of metalloproteinase expression. Certainly, much information is known as to the cis-elements and corresponding trans-activators regulating expression of these genes. We discuss the fact that a number of the metalloproteinase promoters share common structural features and, therefore, not surprisingly are co-regulated in their expression to some extent. More recently, much effort has been devoted to understanding the role of chromatin in regulating gene expression. While this area has been understudied with respect to matrix metalloproteinase (MMP) regulation, the literature indicates a convincing role for both histone modifications and chromatin-remodeling motors in controlling expression of multiple metalloproteinases. In addition to transcriptional control, mRNA stability and protein translation also contribute to the metalloproteinase product amount. We discuss such studies and how various biological cues, including TGF-beta, regulate the levels of certain collagenases either solely through mRNA stabilization or by jointly targeting transcriptional and post-transcriptional mechanisms. We also discuss the current deficits in our knowledge, concerning tissue-specific expression and why despite elevated amounts/activity of trans-activators targeting MMP promoters in tumor cells, nevertheless, MMP expression is largely restricted to the stromal compartment. Finally, we argue for potential technologies to regulate MMP expression of utility in pathological conditions where these enzymes are aberrantly expressed. (c) 2006 Wiley-Liss, Inc.
Publication Types:
Research Support, N.I.H., Extramural
Review
PMID: 17167774 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: Curr Opin Rheumatol. 2006 Jul;18(4):364-8.
Matrix metalloproteinase expression in the spondyloarthropathies.
Zhu J, Yu DT.
Rheumatology Department, Chinese PLA General Hospital, Beijing, China.
PURPOSE OF REVIEW: Expression of matrix metalloproteinases and their tissue inhibitors has been an active area of investigation in rheumatoid arthritis and osteoarthritis. Only recently have investigators started to study these factors in spondyloarthropathy. The purpose of this review is to summarize these recent findings. RECENT FINDINGS: Multiple matrix metalloproteinases and their tissue inhibitors are expressed in the synovial fluid as well as serum samples of spondyloarthropathy patients. Their degrees of expression in the synovia correlate with parameters of arthritis activity such as cell infiltration. In the synovial fluids, the factor which is expressed in very high level is matrix metalloproteinase-3. Two separate cohorts demonstrate that serum levels of matrix metalloproteinase-3 correlate with disease activity in ankylosing spondylitis. Their usefulness appears to exceed those of erythrocyte sedimentation rate and C-reactive protein. Multiple studies also indicate that serum levels of matrix metalloproteinase-3 are suppressed when patients are treated with the anti-tumor necrosis factor-alpha antibody infliximab. SUMMARY: New biomarkers are in demand for spondyloarthropathy in deciding whether patients would benefit from treatment with tumor necrosis factoralpha blockers, monitoring response to treatment, or predicting potential of joint damage if untreated. Recent studies show that among the matrix metalloproteinase and their tissue inhibitors, serum MMP-3 is the one with potential usefulness.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 16763456 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: Front Biosci. 2006 May 1;11:1199-215.
Regulation of matrix metalloproteinase (MMP) gene expression by protein kinases.
Reuben PM, Cheung HS.
Research Service and Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Miami, Florida 33125, USA.
Matrix metalloproteinases (MMPs) are a family of structurally and functionally related zinc-containing endopeptidases that are capable of degrading almost all of the components of the extracellular matrix (ECM). Under physiological and pathological conditions, the MMPs play a significant role in the efficient tissue turnover and remodeling. Specific MMPs are responsible for the matrix degradation and remodeling. Maintenance of the equilibrium between deposition and degradation of the extracellular matrix is essential to the normal tissue development. Therefore, synthesis and breakdown of the MMPs are tightly controlled by protein kinases which mediate a host of other cellular processes. The MMPs are often induced by several agents and any uncontrolled expression of the MMPs can contribute to the pathogenesis of many human diseases. This review focuses on the regulation of the MMPs by the protein kinases at the level of gene expression and their signaling pathways.
Publication Types:
Review
PMID: 16368506 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Nippon Rinsho. 2005 Nov;63 Suppl 11:138-45.
[Helicobacter pylori induces matrix metalloproteinase expression]
[Article in Japanese]
Mori N.
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus.
Publication Types:
Review
PMID: 16363520 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Clin Orthop Relat Res. 2004 Oct;(427 Suppl):S129-37.
Novel inhibitors of matrix metalloproteinase gene expression as potential therapies for arthritis.
Mix KS, Sporn MB, Brinckerhoff CE, Eyre D, Schurman DJ.
Department of Biochemistry, Dartmouth Medical School, Lebanon, NH 03756, USA.
Matrix metalloproteinases are a family of endopeptidases that collectively degrade all components of the extracellular matrix at neutral pH. During the progression of arthritis, MMPs mediate the degradation of cartilage, which consists largely of Type II collagen fibrils and proteoglycans. The collagenases, a subgroup of MMPs, have the singular ability to cleave intact collagens and may provide a rate-limiting step in cartilage destruction. In arthritic lesions, collagenase-1 (matrix metalloproteinase-1) and collagenase-3 (matrix metalloproteinase-13) mediate the irreversible destruction of cartilage, suggesting that these enzymes are therapeutic targets. We describe the role of metalloproteinases in the destruction of connective tissues in arthritis and the treatment strategies that have been developed to block matrix metalloproteinases in an attempt to prevent this destruction. We also discuss novel compounds that may selectively inhibit these cartilage-degrading enzymes, providing opportunities to develop new therapeutic approaches.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 15480055 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
6: Q J Nucl Med. 2003 Sep;47(3):201-8.
Imaging matrix metalloproteinase expression in tumors.
Li WP, Anderson CJ.
Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
metastatic Matrix metalloproteinases (MMPs) are zinc-dependent secreted or transmembrane enzymes constituting a family of over 21 proteolytic members that are capable of selectively digesting a wide spectrum of both extracellular matrix (ECM) and nonmatrix proteins. MMPs play a critical role in tumor growth, angiogenesis, and metastatic processes. MMP inhibitors (MMPIs) have been extensively investigated as anti-tumor drugs, although the clinical trials thus far have been disappointing. In order to better understand the role of MMPs in cancer growth and metastasis, as well as improve the therapeutic efficacy of MMPIs, there is a need to develop new procedures to assess and/or monitor MMP activity in vivo. In addition to determining whether MMPs are present in tumors, it would be desirable to have an imaging agent that better probes other processes associated with MMP overproduction, including angiogenesis and the establishment of the growth of metastatic lesions in distant organ sites. In this paper we review the studies relating to the recent development of in vivo imaging of MMP expression. One of the purposes of this review is to discuss the current status of imaging MMP expression, which includes the types of tracers being developed and the types of imaging modalities available. Although imaging MMP expression is a relatively new area of research, the progress thus far is highly promising.
Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 12897711 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
7: Front Biosci. 2003 Jan 1;8:d78-86.
Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression.
Osteen KG, Igarashi TM, Bruner-Tran KL.
Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. Kevin.osteen@vanderbilt.edu
The endometrium is a unique adult tissue which, in the absence of pregnancy or disease, undergoes cyclic breakdown and regrowth approximately 400 times during a woman's reproductive life. The chances of reproductive success during each cycle depends on appropriate, cell-specific responses to steroids, including expression of matrix metalloproteinases (MMPs). Normal endometrial MMP regulation in response to either estrogen or progesterone requires additional, cell-specific interactions mediated by various growth factors and cytokines. During endometrial maturation, progesterone, retinoic acid and TGF-beta act cooperatively, providing a remarkable biological balance to regulate expression of MMPs in the highly steroid-sensitive endometrium. Exploring the regulatory actions of locally produced growth factors and cytokines on members of the MMP family and their inhibitors will allow a better understanding of the unique physiology of the human endometrium under the influence of progesterone.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 12456342 [PubMed - indexed for MEDLINE]
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8: Methods Mol Med. 2003;74:349-56.
Matrix metalloproteinase expression in lung cancer.
Lim M, Jablons DM.
Thoracic Oncology Program, University of California San Francisco/Mount Zion Medical Center, San Francisco, CA, USA.
Publication Types:
Review
PMID: 12415707 [PubMed - indexed for MEDLINE]
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9: Cardiovasc Res. 2002 Jun;54(3):495-8.
Comment on:
Cardiovasc Res. 2002 Jun;54(3):549-58.
Matrix metalloproteinase-9 expression after myocardial infarction: physiological or pathological?
Thompson MM, Squire IB.
Publication Types:
Comment
Editorial
Review
PMID: 12031694 [PubMed - indexed for MEDLINE]
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10: Ann N Y Acad Sci. 2002 Mar;955:139-46; discussion 157-8, 396-406.
Paracrine mediators of endometrial matrix metalloproteinase expression: potential targets for progestin-based treatment of endometriosis.
Osteen KG, Bruner-Tran KL, Ong D, Eisenberg E.
Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University of Medicine, Nashville, Tennessee 37232, USA. kevin.osteen@mcmail.vanderbilt.edu
The endometrial lining of the human uterus is a highly specialized, steroid-sensitive tissue. Throughout the reproductive years, the endometrium undergoes dramatic cycles of growth, differentiation, and breakdown under the influence of ovarian steroids. In response to changes in steroid exposure throughout the menstrual cycle, the endometrium produces an array of bioactive growth factors and other cytokines that are critical components of paracrine communication. For example, cell-cell communication via paracrine factors directs the expression of matrix metalloproteinases (MMPs), enzymes that mediate tissue remodeling during the menstrual cycle. The disease endometriosis is thought to occur as a consequence of retrograde menstruation, and MMPs appear to contribute to the establishment and progression of ectopic endometrial growth in the peritoneal cavity. Although the risk for developing endometriosis is linked to a woman's steroid exposure, locally produced paracrine factors can modify steroid action on multiple gene targets, including the MMPs. Estrogen-associated growth factors as well as inflammatory cytokines are potent stimulators of MMP expression and may contribute to the ability of endometrial fragments to invade the peritoneal surface and establish ectopic sites of growth. In contrast, paracrine factors associated with progesterone action during early pregnancy inhibit MMP expression and prevent ectopic endometrial growth in an experimental model. For example, locally produced retinoic acid and transforming growth factor-beta (TGF-beta) act in concert with progesterone to suppress MMPs, while enhancing expression of MMP inhibitors (TIMPs) during endometrial differentiation. Targeting pregnancy-associated factors that inhibit endometrial-specific MMP expression and action may enhance the effectiveness of progestin-related treatments for endometriosis.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 11949943 [PubMed - indexed for MEDLINE]
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11: Methods Mol Biol. 2001;151:121-48.
The matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) genes. Transcriptional and posttranscriptional regulation, signal transduction and cell-type-specific expression.
Vincenti MP.
Department of Medicine and Biochemistry, Dartmouth Medical School, Hanover, NH, USA.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 11217296 [PubMed - indexed for MEDLINE]
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12: Matrix Biol. 2000 Dec;19(7):623-9.
Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases.
Ye S.
Human Genetics Research Division, School of Medicine, University of Southampton, UK. shu.ye@soton.ac.uk
The matrix metalloproteinases (MMPs) can degrade a range of extracellular matrix proteins and have been implicated in connective tissue destruction and remodelling associated with cancer invasion and metastasis, cartilage destruction in arthritis, atherosclerotic plaque rupture, and the development of aneurysms. Recently, naturally occurring sequence variation has been detected in the promoter of a number of MMP genes. These genetic polymorphisms have been shown to have allele-specific effects on the transcriptional activities of MMP gene promoters, and to be associated with susceptibility to coronary heart disease, aneurysms and cancers. These findings indicate that variation in the MMP genes may contribute to inter-individual differences in susceptibility to these common, complex diseases, likely through effects on the balance between the synthesis and degradation of extracellular matrix proteins.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 11102751 [PubMed - indexed for MEDLINE]
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13: Gynecol Obstet Invest. 1999;48 Suppl 1:2-13.
Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium.
Osteen KG, Keller NR, Feltus FA, Melner MH.
Women's Reproductive Health Research Center, Vanderbilt University School of Medicine, Nashville, Tenn. 37232, USA. kevin.osteen@mcmail.vanderbilt.edu
Endometrial expression of matrix metalloproteinase (MMP)-3, MMP-7 and MMP-11 occurs during menstrual breakdown and subsequent estrogen-mediated growth, but not during the secretory phase. These enzymes are suppressed by progesterone treatment. Paracrine factors, including transforming growth factor-beta (TGF-beta) and retinoic acid, are also critical for MMP regulation in the endometrium. In contrast, inflammatory cytokines such as interleukin-1alpha may block or interfere with steroid-mediated MMP regulation at ectopic sites of growth. Using in vitro models, our laboratory has investigated the complex interactions between progesterone and locally produced cytokines that may affect MMP expression during the development of endometriosis. Our results indicate that targeting the regulation of MMPs may represent an appropriate therapeutic strategy for the treatment of endometriosis. Copyrightz1999S. KargerAG,Basel
Publication Types:
Review
PMID: 10559659 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
14: FASEB J. 1999 May;13(8):781-92.
Regulation of matrix metalloproteinase expression in tumor invasion.
Westermarck J, Kähäri VM.
MediCity Research Laboratory, Department of Medical Biochemistry, University of Turku, Finland. jukwes@utu.fi
Degradation of basement membranes and stromal extracellular matrix (ECM) is crucial for invasion and metastasis of malignant cells. Degradation of ECM is initiated by proteinases secreted by different cell types participating in tumor cell invasion, and increased expression or activity of every known class of proteinases (metallo-, serine-, aspartic-, and cysteine) has been linked to malignancy and invasion of tumor cells. Studies performed over the last decade have revealed that matrix metalloproteinases (MMPs) play a crucial role in tumor invasion. Expression of MMP genes is transcriptionally regulated by a variety of extracellular factors including cytokines, growth factors, and cell contact to ECM. This review will summarize the current view on the role of MMPs in tumor growth, invasion, and survival, and focus on the role of mitogen-activated protein kinases and AP-1 and ETS transcription factors in the regulation of MMP gene expression during invasion process.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 10224222 [PubMed - indexed for MEDLINE]
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15: Arch Dermatol Res. 1998 Jul;290 Suppl:S47-54.
Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers.
Saarialho-Kere UK.
Department of Dermatology, Helsinki University Central Hospital, Finland. ulpu.saarialho-kere@helsinki.fi
Controlled proteolysis is needed for cell migration, angiogenesis, and matrix remodeling during normal wound repair. Our objective has been to investigate how chronic leg ulcers differ from normally healing wounds (pinch graft donor sites) with respect to their metalloproteinase expression patterns. Using in situ hybridization and immunohistochemistry, we found that collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) were expressed in keratinocytes bordering both acute and chronic wounds. Unlike MMP-1, signal for collagenase-3 (MMP-13) was not detected in keratinocytes but exclusively in fibroblasts deep in the ulcer bed of chronic wounds, suggesting that while MMP-1 production is important for migration, MMP-13 plays a role in matrix remodeling. Tissue inhibitor of metalloproteinase (TIMP)-1 was not detected in the epidermis of any chronic wound sample while it was expressed in keratinocytes bordering normally healing wounds. TIMP-3 was abundantly expressed in stromal fibroblast- and macrophage-like cells surrounding vessels and sweat glands in both types of wounds. Our results suggest that there are no qualitative differences in the expression of MMPs-1, -3 and -10 in the epidermis of chronic vs normally healing wounds. However, the number of stromal cells expressing MMP-1 and MMP-3 was greater in chronic vs acute wounds, whereas MMP-10 was never detected in the dermis. TIMP-1 expression near the basement membrane in acute, but not in chronic, wounds suggests that the balance between MMPs and their inhibitors may be altered in poorly healing wounds. Analogous to chronic cutaneous wounds, MMP-1 and -3 are abundantly expressed in chronic small and large bowel ulcers, while the migrating surface epithelium is negative for TIMP-1 expression.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 9710383 [PubMed - indexed for MEDLINE]
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16: Semin Reprod Endocrinol. 1996 Aug;14(3):247-55.
Steroid and growth factor regulation of matrix metalloproteinase expression and endometriosis.
Osteen KG, Bruner KL, Sharpe-Timms KL.
Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Publication Types:
Review
PMID: 8885055 [PubMed - indexed for MEDLINE]
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17: Gene Expr. 1996;6(4):197-207.
Nuclear hormone receptors inhibit matrix metalloproteinase (MMP) gene expression through diverse mechanisms.
Schroen DJ, Brinckerhoff CE.
Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.
Agents like retinoids, thyroid hormone, glucocorticoids, progesterone, androgens, which bind to members of the nuclear receptor superfamily, inhibit the synthesis of matrix metalloproteinases (MMPs) in many cell types. These Zn2(+)- and Ca2(+)-dependent MMPs degrade components of the extracellular matrix (ECM), and precise regulation of their expression is crucial in many normal processes. However, inappropriate expression of MMPs contributes to a variety of invasive and erosive diseases, and inhibition of MMP synthesis provides an important mechanism for controlling such aberrant or dysregulated responses. Nuclear receptors control MMPs through a variety of seemingly redundant mechanisms. First, nuclear receptors act on the promoters of MMP genes to enhance or suppress trans-activation. Ironically, in a family of genes that exhibits substantial regulation by nuclear receptors, few consensus hormone responsive elements (HREs) have been deomonstrated in MMP promoters. Rather, inhibition of MMPs occurs primarily, but not exclusively, at AP-1 sites. Here, nuclear receptors form complexes on the DNA through interactions with AP-1 proteins, sequester Fos/Jun and/or decrease the mRNAs for these transcription factors. Second, nuclear receptors and their ligands can indirectly inhibit MMPs. For instance, both retinoids and glucocorticoids induce the transcription of TIMPs (tissue inhibitor of metalloproteinases), which complex with MMPs and inhibit enzymatic activity, and progesterone stimulates production of transforming growth factor-beta (TGF-beta), which in turn suppresses MMP-7 (matrilysin). Finally, nuclear receptors bind to coactivators, corepressors, and components of the general transcriptional apparatus, but the potential role of these interactions in MMP regulation remains to be determined. We conclude that nuclear receptors utilize multiple, apparently redundant, mechanisms to inhibit MMP gene expression, assuring precise control of ECM degradation under a variety of physiologic and pathologic conditions.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 9196075 [PubMed - indexed for MEDLINE]
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18: Crit Rev Eukaryot Gene Expr. 1996;6(4):391-411.
Regulating expression of the gene for matrix metalloproteinase-1 (collagenase): mechanisms that control enzyme activity, transcription, and mRNA stability.
Vincenti MP, White LA, Schroen DJ, Benbow U, Brinckerhoff CE.
Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.
Matrix metalloproteinase-1 (MMP-1) is one of three collagenases that can degrade the interstitial collagens, types I, II, and III at neutral pH. As these collagens are the most abundant proteins in the body, collagenase plays a critical role in modeling and remodeling the extracellular matrix. Therefore, it is not surprising that MMP-1 gene expression can be regulated at multiple points. Procollagenase can be activated by mechanisms that generate an active enzyme with differing specific activities, and the active enzyme can be inhibited by complexing with either the tissue inhibitor of metalloproteinases (TIMPs) or alpha 2 macroglobulin. The activator protein-1 (AP-1) site in the collagenase promoter plays a prominent role in the transcriptional control of the collagenase gene. It is essential for basal transcription, and contributes to induction by phorbol esters, although other sites in the proximal promoter are essential. In contrast, transactivation by cytokines such as Interleukin-1 depends on sequences in more distal regions of the promoter. Posttranscriptional mechanisms also regulate gene expression, and several cytokines and growth factors increase the stability of the collagenase transcript. Finally, glucocorticoid hormones repress transcription of the collagenase gene by the interaction of glucocorticoid receptors with the AP-1 proteins, Fos and Jun. Retinoids also suppress transcription by mechanisms that involve down-regulation of fos and jun mRNA, sequestration of Fos and Jun proteins, and the formation of complexes of retinoic acid receptors (RAR/RXR heterodimers) and AP-1 proteins on the DNA. These multiple points of regulation assure precise control of collagenolytic activity in a variety of physiologic and pathologic conditions.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 8959374 [PubMed - indexed for MEDLINE]
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19: Ann N Y Acad Sci. 1994 Sep 6;732:42-50.
Matrix metalloproteinase gene expression.
Matrisian LM.
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 7978826 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
20: Immun Infekt. 1993 Apr;21 Suppl 1:20-1.
[The matrix metalloproteinase gene family: structure, function, expression, and role in destructive joint disease]
[Article in German]
Conca W.
Abteilung Rheumatologie und Klinische Immunologie, Medizinische Universitätsklinik Freiburg.
The matrix metalloproteinases, i.e. collagenases, gelatinases and stromelysins, are members of a gene family. They are capable of degrading every component of the extracellular matrix. Tissue destruction observed in inflammatory joint disease is largely accounted for by the action of these enzymes. Among the most potent inducers of metalloproteinase expression are the inflammatory cytokines IL-1 and TNF-alpha. Studies of mechanisms of induction by these mediators at the transcriptional level have improved our understanding of the biological controls of metalloproteinase synthesis. Cytokine inhibitors might serve to inhibit or postpone the crippling consequences of metalloproteinase action.
Publication Types:
English Abstract
Review
PMID: 8344678 [PubMed - indexed for MEDLINE]
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