Huttenlocher A, Werb Z, Tremble P, Huhtala P, Rosenberg L, Damsky C H
Department of Stomatology, University of California, San Francisco, USA.
Matrix Biol. 1996 Sep;15(4):239-50. doi: 10.1016/s0945-053x(96)90115-8.
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.
玻连蛋白是血浆和细胞外基质中的一种主要细胞黏附分子，它通过整合素αV家族介导细胞黏附和铺展。在本研究中，我们证明了核心蛋白聚糖（一种小分子硫酸皮肤素蛋白聚糖）可调节兔滑膜成纤维细胞在黏附于玻连蛋白时的细胞外基质重塑。当核心蛋白聚糖与玻连蛋白或纤连蛋白的120 kDa细胞结合结构域共同存在于底物上时，可诱导基质金属蛋白酶胶原酶（MMP-1）的表达，但与完整的纤连蛋白或I型胶原共同存在时则不会。在黏附后8小时内即可检测到分泌的胶原酶，在黏附于核心蛋白聚糖加玻连蛋白的细胞中，细胞形状或黏着斑形成没有相关改变，而在黏附于核心蛋白聚糖加纤连蛋白120 kDa片段的细胞中观察到细胞变圆。核心蛋白聚糖的核心蛋白而非糖胺聚糖部分足以在两种底物上诱导胶原酶表达；然而，在黏附于纤连蛋白120 kDa结构域的细胞中观察到的细胞变圆，需要核心蛋白聚糖的糖胺聚糖部分以及核心蛋白。核心蛋白聚糖的胶原酶诱导作用似乎与其对转化生长因子-β的作用无关，因为针对转化生长因子-β的功能阻断抗体不会干扰核心蛋白聚糖的胶原酶诱导作用。这些数据表明，当核心蛋白聚糖与玻连蛋白或纤连蛋白的120 kDa片段共同存在于基质中时，在细胞中具有特定的基因调节作用，这些多肽存在于活跃重塑的组织中。因此，这些黏附调节分子共同转导可能有助于形态发生、伤口愈合和疾病状态下组织重塑过程的新信号。
