1: Pathol Biol (Paris). 2006 Sep;54(7):387-95. Epub 2006 Sep 7.


The effects of the Maillard reaction on the physical properties and cell interactions of collagen.

Avery NC, Bailey AJ.

Collagen Research Group, University of Bristol, Langford, BS40 5DU Bristol, UK.

The non-enzymic glycation of collagen occurs as its turnover decreases during maturation, with complex carbohydrates accumulating slowly and the end-products of these reactions being permanent. The nature of these advanced glycation end-reaction products (AGEs) can be categorised as: 1) cross-linking: intermolecular cross-linking may occur between two adjacent molecules and involve lysine to lysine or lysine to arginine residues. Several compounds have been characterised. They are believed to be located between the triple helical domains of adjacent molecules in the fibre resulting in major changes of the physical properties, primarily, fibre stiffness, thermal denaturation temperature and enzyme resistance, all of which increase slowly with age but the rate is accelerated in diabetes mellitus due to high glucose levels: 2) side-chain modifications: these changes alter the charge profile of the molecule affecting the interactions within the fibre and if they occur at specific sites can affect the cell-collagen interaction. Modification of arginine within the sites RGD and GFOGER recognised by the two specific integrins (alpha1beta2 and alpha2beta1) for collagen reduce cell interactions during turnover and for platelet interactions (alpha1beta2). These changes can ultimately affect repair of, for example, vascular damage and dermal wound healing in diabetes mellitus. Both types of modification are deleterious to the optimal properties of collagen as a supporting framework structure and as a controlling factor in cell matrix interactions. Glycation during ageing and diabetes is therefore responsible for malfunctioning of the diverse collagenous tissues throughout the body.

Publication Types:
Review

PMID: 16962252 [PubMed - indexed for MEDLINE]

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2: J Soc Biol. 2005;199(4):329-36.


[Functional interactions between the TGF-beta signaling pathway via the Smads and TNF-alpha: implications for the regulation of type I collagen expression]

[Article in French]

Verrecchia F.

INSERM U697, Hôpital Saint-Louis, Pavillon Bazin, 1, avenue Claude Vellefaux, 75010 Paris. franck.verrecchia@stlouis.inserm.fr

The balance between production and degradation of type I collagen plays a critical role in the development and maintenance of organ and tissue integrity. Its also represents the most crucial element governing the process of tissue repair. TGF-beta, a key player in the physiopathology of tissue repair, enhances type I collagene gene expression. In contrast, TNF-alpha, whose matrix-remodelling function is opposite to that of TGF-beta, reduces type I collagen gene expression. This review focuses on transcriptional regulation of type I collagen by TGF-beta and TNF-alpha, and on the molecular mechanisms that control the antagonistic activity of TNF-alpha against TGF-beta-driven type I collagen gene expression.

Publication Types:
English Abstract
Review

PMID: 16738527 [PubMed - indexed for MEDLINE]

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3: J Biomed Opt. 2006 Jan-Feb;11(1):014003.


Molecular interactions of exogenous chemical agents with collagen--implications for tissue optical clearing.

Yeh AT, Hirshburg J.

Texas A&M University, Department of Biomedical Engineering, 337 Zachry Engineering Center, 3120 TAMU, College Station, Texas 77843, USA. ayeh@tamu.edu

Reduction of optical scattering in turbid biological tissues using nonreactive chemical agents has potential applications for light-based diagnostics and therapeutics. Optical clearing effects by exogenous chemical agents, in particular sugars and sugar alcohols, have been found to be temporary with tissue rehydration. Applications with dermatologic laser therapies are now being investigated, but suffer from the inability of studied agents to penetrate the superficial layers of human skin. Selection, design, and refinement of topically effective chemical agents are hindered by a lack of fundamental understanding of tissue clearing mechanisms. We present recent work, particularly from the biochemistry community, detailing molecular interactions between chemical agents and collagen. This body of work demonstrates the perturbative effects of sugars and sugar alcohols on collagen high-order structures at micro- and nanometer length scales by screening noncovalent bonding forces. In addition, these studies emphasize the nonreactive nature of agent-collagen interactions and the ability of noncovalent bonding forces to recover with agent removal and drive reassembly of destabilized collagen structures. A mechanism of tissue optical clearing is proposed based on agent destabilization of high-order collagen structures.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

PMID: 16526880 [PubMed - indexed for MEDLINE]

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4: Int J Biochem Cell Biol. 2004 Jun;36(6):1115-25.


Erratum in:
Int J Biochem Cell Biol. 2005 Jan;37(1):239-40.

The role of thrombospondins 1 and 2 in the regulation of cell-matrix interactions, collagen fibril formation, and the response to injury.

Bornstein P, Agah A, Kyriakides TR.

Department of Biochemistry, Box 357350, University of Washington, Seattle, WA 98195, USA. bornsten@u.washington.edu

Thrombospondins (TSPs) 1 and 2 are extracellular modular glycoproteins that are best known for their anti-angiogenic properties and their ability to modulate cell-matrix interactions. However, these proteins, and in particular TSP2, are pleiotropic in function and affect processes as disparate as bone growth and hemostasis. In recognition of their ability to influence a wide variety of cell functions, and in the absence of convincing evidence for their participation as integral components of extracellular structures, the term 'matricellular' has been applied to these and a small group of functionally related proteins. In this review, we focus on the role of TSP1 and 2 in two forms of injury in mice, excisional skin wounds and subcutaneously implanted biomaterials, and take advantage of mice with targeted disruptions of one or both genes to identify likely biochemical mechanisms that could account for the characteristics of the injury response in these knockout mice. In work that stems largely from our own laboratory, we show that pericellular levels of the matrix metalloproteinase, MMP2, are controlled to a large extent by TSP2 (and potentially also by TSP1), and that elevated levels of MMP2 are likely to account in part for defects as diverse as reduced cellular adhesion, abnormal collagen fibril structure, and increased endothelial cell and vascular proliferation.

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: 15094126 [PubMed - indexed for MEDLINE]

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5: Biochem Soc Symp. 2003;(70):81-94.


Collagen-platelet interactions: recognition and signalling.

Farndale RW, Siljander PR, Onley DJ, Sundaresan P, Knight CG, Barnes MJ.

Department of Biochemistry, University of Cambridge, Downing Site, Cambridge CB2 1QW, U.K. rwf10@cam.ac.uk

The collagen-platelet interaction is central to haemostasis and may be a critical determinant of arterial thrombosis, where subendothelium is exposed after rupture of atherosclerotic plaque. Recent research has capitalized on the cloning of an important signalling receptor for collagen, glycoprotein VI, which is expressed only on platelets, and on the use of collagen-mimetic peptides as specific tools for both glycoprotein VI and integrin alpha 2 beta 1. We have identified sequences, GPO and GFOGER (where O denotes hydroxyproline), within collagen that are recognized by the collagen receptors glycoprotein VI and integrin alpha 2 beta 1 respectively, allowing their signalling properties and specific functional roles to be examined. Triple-helical peptides containing these sequences were used to show the signalling potential of integrin alpha 2 beta 1, and to confirm its important contribution to platelet adhesion. Glycoprotein VI appears to operate functionally on the platelet surface as a dimer, which recognizes GPO motifs that are separated by four triplets of collagen sequence. These advances will allow the relationship between the structure of collagen and its haemostatic activity to be established.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 14587284 [PubMed - indexed for MEDLINE]

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6: Platelets. 2000 Aug;11(5):252-8.


Update on collagen receptor interactions in platelets: is the two-state model still valid?

Watson S, Berlanga O, Best D, Frampton J.

Department of Pharmacology, University of Oxford, UK.

This review summarises some of the key developments that have taken place in our understanding of platelet-collagen interactions within the last 18 months. Within this time, the major activatory collagen receptor glycoprotein VI (GPVI) has been sequenced and shown to reconstitute collagen responses in a megakaryocytic cell line. It is a member of the Ig superfamily of proteins, with two extracellular Ig domains, and is constitutively associated with the Fc receptor gamma-chain (FcR gamma-chain). GPVI signals through a pathway that shares many features with those of immune receptors, with critical roles for Syk and the adapters LAT and SLP-76 in the activation of PLCgamma2. Significant developments have also taken place in regard to the role of the major adhesion receptor for collagen, the integrin alpha2beta1 (also known as GPIa-IIa). An alpha2beta1-selective collagen-based peptide has been developed and co-crystallised with the I-domain of the alpha2 subunit. Polymorphisms in alpha2 have been shown to cause wide variation in expression of alpha2beta1, with the alpha2 allele T807/A873 leading to a high level of the integrin and increased risk of stroke in young people. Activation of platelets by a wide range of agonists has been shown to increase the affinity of alpha2beta1 to intermediate or high affinity states. This has important implications for the two-site, two-state model of collagen-platelet interactions. A new model is proposed in which collagen binds initially to either alpha2beta1 or GPVI, leading to subsequent binding to the other receptor and conversion of the integrin to a high affinity state. In this model, both receptors generate intracellular signals which support platelet activation.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 11030459 [PubMed - indexed for MEDLINE]

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7: Micron. 2001 Apr;32(3):223-37.


Type V collagen: heterotypic type I/V collagen interactions in the regulation of fibril assembly.

Birk DE.

Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, 1020 Locust Street, JAH 543, Philadelphia, PA 19107, USA. david.birk@mail.tju.edu

Type V collagen is a quantitatively minor fibrillar collagen with a broad tissue distribution. The most common type V collagen isoform is alpha1(V)(2) alpha2(V) found in cornea. However, other isoforms exist, including an [alpha1(V)alpha2(V)alpha3(V)] form, an alpha1(V)(3) homotrimer and hybrid type V/XI forms. The functional role and fibrillar organization of these isoforms is not understood. In the cornea, type V collagen has a key role in the regulation of initial fibril assembly. Type I and type V collagen co-assemble into heterotypic fibrils. The entire triple-helical domain of the type V collagen molecules is buried within the fibril and type I collagen molecules are present along the fibril surface. The retained NH(2)-terminal domains of the type V collagen are exposed at the surface, extending outward through the gap zones. The molecular model of the NH(2)-terminal domain indicates that the short alpha helical region is a flexible hinge-like region allowing the peptide to project away from the major axis of the molecule; the short triple-helical regions serve as an extension through the hole zone, placing the tyrosine-rich domain at the surface. The assembly of early, immature fibril intermediates (segments) is regulated by the NH(2)-terminal domain of type V collagen. These NH(2)-terminal domains alter accretion of collagen molecules onto fibrils and therefore lateral growth. A critical density would favor the initiation of new fibrils rather than the continued growth of existing fibrils. Other type V collagen isoforms are likely to have an important role in non-cornea tissues. This role may be mediated by supramolecular aggregates different from those in the corneal stroma or by an alteration of the interactions mediated by tissue-specific type V collagen domains generated by different isoforms or aggregate structures. Presumably, the aggregate structure or specific domains are involved in the regionalization of fibril-associated macromolecules necessary for the tissue-specific regulation of later fibril growth and matrix assembly stages.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 11006503 [PubMed - indexed for MEDLINE]

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8: Eur J Clin Invest. 1999 Dec;29(12):1066-76.


Review article: platelet-collagen interactions: membrane receptors and intracellular signalling pathways.

Alberio L, Dale GL.

Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. lalberio@access.ch

Platelet adhesion to and activation by exposed subendothelial collagen plays a critical role in normal haemostasis and pathological thrombosis. Recent advances in elucidating the mechanisms underlying platelet-collagen interaction support a 'two-site, two-step' model. Direct platelet binding to integrin alpha2beta1 mainly sustains adhesion and allows recognition of glycoprotein VI. The latter interaction is responsible for characteristic intracellular signalling events leading to p72Syk and PLCgamma2 activation. The present review describes the known collagen receptors on platelets and discusses the current understanding of signal transduction promoted by collagen.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 10583456 [PubMed - indexed for MEDLINE]

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9: Cell Mol Life Sci. 1997 Jun;53(6):539-45.


Annexin V interactions with collagen.

von der Mark K, Mollenhauer J.

Institute of Experimental Medicine, Friedrich-Alexander University of Erlangen-Nürnberg, Germany. kvdmark@EXPMED.UNI-ERLANGEN.DE

Annexin V was originally identified as a collagen-binding protein called anchorin CII and was isolated from chondrocyte membranes by affinity chromatography on native type II collagen. The binding of annexin V to native collagen type II is stable at physiological ionic strength when annexin V is reconstituted in liposomes. The binding to native collagen types II and X, and to some extent to type I as well, was confirmed using recombinant annexin V. A physiological role for annexin V interactions with extracellular collagen is consistent with the localization of annexin V on the outer cell surface of chondrocytes, microvilli of hypertrophic chondrocytes, fibroblasts and osteoblasts. A breakthrough in our understanding of the function of annexin V was made with the discovery of its calcium channel activity. At least one of several putative functions of annexin V became obvious from studies on matrix vesicles derived from calcifying cartilage. It was found that calcium uptake by matrix vesicles depend on collagen type II and type X binding to annexin V in the vesicles and was lost when collagens were digested with collagenase: calcium influx was reconstituted after adding back native collagen II or V. These findings indicate that annexin V plays a major role in matrix vesicle-initiated cartilage calcification as a collagen-regulated calcium channel.

Publication Types:
Review

PMID: 9230933 [PubMed - indexed for MEDLINE]

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10: Int Rev Cytol. 1997;173:73-156.


Basement-membrane stromal relationships: interactions between collagen fibrils and the lamina densa.

Adachi E, Hopkinson I, Hayashi T.

Department of Anatomy and Cell Biology, Kitasato University School of Medicine, Kanagawa, Japan.

Collagens, the most abundant molecules in the extracellular space, predominantly form either fibrillar or sheet-like structures-the two major supramolecular conformations that maintain tissue integrity. In connective tissues, other than cartilage, collagen fibrils are mainly composed of collagens I, III, and V at different molecular ratios, exhibiting a D-periodic banding pattern, with diameters ranging from 30 to 150 nm, that can form a coarse network in the extracellular matrix in comparison with a fine meshwork of lamina densa. The lamina densa represents a stable sheet-like meshwork composed of collagen IV, laminin, nidogen, and perlecan compartmentalizing tissue from one another. We hypothesize that the interactions between collagen fibrils and the lamina densa are crucial for maintaining tissue-tissue interactions. A detailed analysis of these interactions forms the basis of this review article. Here, we demonstrate that there is a direct connection between collagen fibrils and the lamina densa and propose that collagen V may play a crucial role in this connection. Collagen V might also be involved in regulation of collagen fibril diameter and anchoring of epithelia to underlying connective tissues.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 9127952 [PubMed - indexed for MEDLINE]

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11: Semin Thromb Hemost. 1995;21(2):123-9.


Platelet-collagen interactions.

Kehrel B.

Department of Internal Medicine, University of Münster, Germany.

The collagens belong to the constituents of the subendothelium that determine the thrombogenicity of the vessel wall. The existence of several genetically distinct collagens is well documented. To date, 19 collagens have been characterized. The collagens are divided into the fibril forming collagens and the non-fibril forming collagens. At least nine of the different collagens--type I, III, IV, V, VI, VIII, XII, XIII, XIV--were found in the vessel wall. All collagen molecules are built of three chains in a triple-helical conformation. Some collagens also contain large parts of non-collagenous domains. An interesting example for complex collagens is collagen type VI for it shares non-collagenous domains with the von Willebrand factor A domain, the platelet glycoprotein Ib, fibronectin type III repeats, and Kunitz type protease inhibitor. Monomeric and fibrillar collagens effectively support platelet adhesion, whereas for collagen-induced platelet aggregation and secretion, the native, triple-helical structure of collagen is required. The platelet reactive sites in collagens type I and III have been studied intensively. Using CNBr-peptides three aggregatory sites in the alpha 1(I) chain and one in the alpha 1(III) chain have been found. Cyanogen bromide fragments of collagen type I were also used to measure platelet adhesion under flow conditions. alpha 1(I)CB3 strongly supports platelet adhesion. The two peptides alpha 1(I)CB3 and alpha 1(III)CB4 are highly homologous. alpha 1(III)CB4 is highly aggregatory. Several substances are known to interfere at different levels with the platelet-collagen interactions and have been identified in blood-feeding animals. Among them are the "leech anti-platelet protein" (LAPP), calin, moubatin, and pallidipin.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 7660134 [PubMed - indexed for MEDLINE]

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12: Tumour Biol. 1993;14(3):137-43.


Tumor cell interactions with stromal elastin and type I collagen: the consequences of specific adhesion and proteolysis.

Parsons DF.

Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.

Elastin and collagen are abundant fibrous molecules in the stroma. Tumor cells invading the stroma are in contact with fibers of both types much of the time. Both may serve as footholds for the traction required for movement. Elastin has an additional role. Elastin peptides are known to stimulate receptor signaling and chemotaxis, which could explain the morphometric changes (membrane and organelle polarization and cell volume shrinkage) that we have reported for certain tumor cell lines invading elastic lamina. Elastin and its peptides emerge as possible invasion enhancers for some tumor cells. In ongoing work we are screening human tumors that contact elastin (e.g., breast carcinomas) to see if the presence of elastin receptors correlates with early dissemination of metastatic tumor cells.

Publication Types:
Review

PMID: 8210947 [PubMed - indexed for MEDLINE]

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13: Biochem Soc Trans. 1991 Nov;19(4):877-81.


Proteoglycan: collagen interactions and corneal ultrastructure.

Scott JE.

Chemical Morphology, Manchester University, U.K.

Publication Types:
Review

PMID: 1794577 [PubMed - indexed for MEDLINE]

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14: Int J Biol Macromol. 1991 Jun;13(3):157-61.


Proteoglycan: collagen interactions in connective tissues. Ultrastructural, biochemical, functional and evolutionary aspects.

Scott JE.

Chemical Morphology, Cell and Structural Biology, Manchester University, UK.

Electron histochemical investigations of mammalian and echinoderm tissues, using cupromeronic blue to stain proteoglycans (PGs) specifically in critical electrolyte concentration methods, showed that collagen fibrils are associated with keratan sulphate and chondroitin (dermatan) sulphate ('tadpole') PGs at the a, c, d and e bands on the fibril surface, giving rise to the 'one proteoglycan: one binding site' hypothesis. Intra-fibrillar PGs have been observed, distributed in a regular way which suggests that collagen fibrils are aggregates of 'protofibrils', some of which carry PGs at their surfaces. A scheme for remodelling of collagen fibrils, based on recycling of these protofibrils, is outlined. The choice of which tadpole PG to use to carry out a given function is decided to a considerable extent by the availability of oxygen to the relevant tissue element.

Publication Types:
Review

PMID: 1911556 [PubMed - indexed for MEDLINE]

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15: Biochem J. 1988 Jun 1;252(2):313-23.


Proteoglycan-fibrillar collagen interactions.

Scott JE.

Manchester University, U.K.

Publication Types:
Review

PMID: 3046606 [PubMed - indexed for MEDLINE]

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16: Ciba Found Symp. 1984;108:25-43.


Laminin, proteoglycan, nidogen and collagen IV: structural models and molecular interactions.

Timpl R, Fujiwara S, Dziadek M, Aumailley M, Weber S, Engel J.

Major components of basement membranes, including collagen IV, laminin, heparan sulphate proteoglycan and nidogen, were isolated from the matrix of the EHS sarcoma. The purified components were analysed for their domain structure and for the participation of distinct domains in molecular interactions and cell binding. Collagen IV consists of four domains which have triple helical or non-collagenous structures. Self-assembly of the protein into a network-like organization occurs by specific interactions between N-terminal triple helical segments and between the C-terminal globules. Cell binding requires a central triple helical segment. Laminin has the shape of an asymmetrical cross; different globular domains within this structure mediate binding to proteoglycan and to cells. The proteoglycan consists of four heparan sulphate chains attached to a small protein core. These chains have the potential to bind laminin, fibronectin and collagen IV. Nidogen was isolated in several molecular forms which showed either self-aggregation or binding to laminin.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 6440757 [PubMed - indexed for MEDLINE]

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17: Compr Ther. 1977 Jun;3(6):59-66.


Platelet-collagen interactions.

Legrand Y, Fauvel F, Caen JP.

Publication Types:
Review

PMID: 326470 [PubMed - indexed for MEDLINE]