Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions
Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions
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DOI：
10.1091/mbc.e02-01-0048
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发表时间：
2002-10-01
影响因子：
3.3
通讯作者：
Hocking, DC
中科院分区：
文献类型：
--
作者：
Sottile, J;Hocking, DC
细胞外基质的重塑发生在发育、伤口愈合和各种病理过程中，包括动脉粥样硬化、缺血性损伤和血管生成。因此，确定组织重塑过程中控制基质沉积和降解之间平衡的因素对于理解调节各种正常和病理过程的机制至关重要。使用无纤连蛋白的细胞，我们发现纤连蛋白聚合到细胞外基质中是胶原蛋白-I和血小板反应蛋白-1的沉积所必需的，并且细胞外基质纤连蛋白原纤维的维持需要纤连蛋白基质的持续聚合。此外，在没有纤连蛋白沉积的情况下，单独的整联蛋白连接不足以维持细胞外基质纤连蛋白。我们的数据还表明，血小板反应蛋白-1 和胶原蛋白 I 保留在细胞外基质内的纤维结构中取决于完整的纤连蛋白基质。完整的纤连蛋白基质对于维持细胞基质粘附位点的组成也至关重要。在没有纤连蛋白和纤连蛋白聚合的情况下，α5β1整联蛋白和张力蛋白都不定位于纤维细胞-基质粘附位点。这些数据表明纤连蛋白聚合是细胞外基质组织和稳定性的关键调节剂。纤连蛋白聚合作为控制细胞外基质和细胞-基质粘附位点的组织和组成的开关的能力，为细胞提供了一种精确控制细胞-细胞外基质信号转导事件的方法，这些信号转导事件调节细胞行为的许多方面，包括细胞增殖、迁移和分化。
Remodeling of extracellular matrices occurs during development, wound healing, and in a variety of pathological processes including atherosclerosis, ischemic injury, and angiogenesis. Thus, identifying factors that control the balance between matrix deposition and degradation during tissue remodeling is essential for understanding mechanisms that regulate a variety of normal and pathological processes. Using fibronectin-null cells, we found that fibronectin polymerization into the extracellular matrix is required for the deposition of collagen-I and thrombospondin-1 and that the maintenance of extracellular matrix fibronectin fibrils requires the continual polymerization of a fibronectin matrix. Further, integrin ligation alone is not sufficient to maintain extracellular matrix fibronectin in the absence of fibronectin deposition. Our data also demonstrate that the retention of thrombospondin-1 and collagen I into fibrillar structures within the extracellular matrix depends on an intact fibronectin matrix. An intact fibronectin matrix is also critical for maintaining the composition of cell-matrix adhesion sites; in the absence of fibronectin and fibronectin polymerization, neither alpha5beta1 integrin nor tensin localize to fibrillar cell-matrix adhesion sites. These data indicate that fibronectin polymerization is a critical regulator of extracellular matrix organization and stability. The ability of fibronectin polymerization to act as a switch that controls the organization and composition of the extracellular matrix and cell-matrix adhesion sites provides cells with a means of precisely controlling cell-extracellular matrix signaling events that regulate many aspects of cell behavior including cell proliferation, migration, and differentiation.