DECORIN REGULATES COLLAGENASE GENE-EXPRESSION IN FIBROBLASTS ADHERINGTO VITRONECTIN

Vitronectin, a principal cell adhesion molecule in plasma and extracel lular matrix, mediates cell adhesion and spreading via the alpha V fam ily of integrins. In this study we demonstrate that decorin, a small d ermatan sulfate proteoglycan, regulates extracellular matrix remodelin g in rabbit synovial fibroblasts adhering to vitronectin. Decorin indu ced the expression of the matrix metalloproteinase collagenase (MMP-1) when present on the substrate with vitronectin, or with the 120-kDa c ell-binding domain of fibronectin, but not when present with intact fi bronectin 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 observe d in cells adhering to the 120-kDa domain of fibronectin. The collagen ase-inducing effect of decorin seems to be independent of its effects on transforming growth factor-beta, as function-blocking antibodies ag ainst transforming growth factor-p did not-interfere with the collagen ase-inducing effects of decorin. These data indicate that decorin has specific gene regulatory effects in cells when present in the matrix w ith vitronectin or the 120-kDa fragment of fibronectin, polypeptides t hat are present in actively remodeling tissues. Thus, in combination, these adhesion regulatory molecules transduce novel signals that may c ontribute to the tissue remodeling process in morphogenesis, wound hea ling and disease states.