Decorin regulates collagenase gene expression in fibroblasts adhering to vitronectin.
Vitronectin, a principal cell adhesion molecule in plasma and extracellular matrix, mediates cell adhesion and spreading via the alpha V family of integrins. In this study we demonstrate that decorin, a small dermatan sulfate proteoglycan, regulates extracellular matrix remodeling in rabbit synovial fibroblasts adhering to vitronectin. Decorin induced the expression of the matrix metalloproteinase collagenase (MMP-1) when present on the substrate with vitronectin, or with the 120-kDa cell-binding domain of fibronectin, but not when present with intact fibronectin or Type I collagen. Secreted collagenase was detected within 8 h of adhesion, there was no associated alteration in cell shape or focal contact formation in cells adhering to decorin plus vitronectin, whereas cell rounding was observed in cells adhering to decorin plus the 120-kDa fragment of fibronectin. The core protein of decorin, but not the glycosaminoglycan moiety, was sufficient to induce collagenase expression on both substrates; however, the glycosaminoglycan moiety of decorin as well as the core were required for cell rounding observed in cells adhering to the 120-kDa domain of fibronectin. The collagenase-inducing effect of decorin seems to be independent of its effects on transforming growth factor-beta, as function-blocking antibodies against transforming growth factor-beta did not interfere with the collagenase-inducing effects of decorin. These data indicate that decorin has specific gene regulatory effects in cells when present in the matrix with vitronectin or the 120-kDa fragment of fibronectin, polypeptides that are present in actively remodeling tissues. Thus, in combination, these adhesion regulatory molecules transduce novel signals that may contribute to the tissue remodeling process in morphogenesis, wound healing and disease states.
Huttenlocher
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Department of Stomatology, University of California, San Francisco, USA.
Werb
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Tremble
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Huhtala
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Rosenberg
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Damsky
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D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D058578:Biglycan; D002448:Cell Adhesion; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis*; D058575:Decorin; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007700:Kinetics; D020781:Matrix Metalloproteinase 1; D011509:Proteoglycans / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology; D019096:Vitronectin
D000906:Antibodies; D058578:Biglycan; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019096:Vitronectin; D017364:Collagenases; D020781:Matrix Metalloproteinase 1