The fibronectin synergy site modulates TGF-β-dependent fibroblast contraction
The fibronectin synergy site modulates TGF-β-dependent fibroblast contraction
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DOI：
10.1016/j.bbrc.2007.06.121
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发表时间：
2007-09-07
影响因子：
3.1
通讯作者：
Van De Water, Livingston
中科院分区：
文献类型：
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作者：
Meckmongkol, Teerin T.;Harmon, Robert;Van De Water, Livingston
损伤后的组织重塑涉及tgf - β介导的成纤维细胞收缩。虽然这些细胞嵌入富含纤维连接蛋白（FN）的基质中，但FN细胞相互作用在这一过程中的作用尚不完全清楚。为了探讨FN基质呈递的作用，我们分析了tgf - β对粘附在FN包被的聚丙烯酰胺凝胶（PAG）上的成纤维细胞的影响。令人惊讶的是，在这些条件下，tgf - β触发细胞圆缩。这伴随着Rho活化和MLC磷酸化的增加，并通过抑制Rho激酶而逆转。虽然已知成纤维细胞与纤维连接蛋白的RGD和协同位点结合，但它们对细胞功能的相对贡献尚不清楚。当FN的协同位点被阻断时，MLC磷酸化减少，细胞收缩逆转，表明除了tgf - β介导的Rho激活外，收缩还需要来自协同位点的信号。因此，在治疗上调节FN协同位点可能为组织修复过程中调节收缩力提供了一种机制。(c) 2007爱思唯尔公司版权所有。
Tissue remodeling following injury involves TGF-beta-mediated fibroblast contraction. While these cells are embedded in a fibronectin (FN)-rich matrix, the role of FN-cell interactions in this process is not fully understood. To explore the role of FN matrix presentation, we analyzed the effect of TGF-beta on fibroblasts adhered to FN-coated polyacrylamide gels (PAG). Surprisingly, under these conditions TGF-beta triggered cell rounding/contraction. This was accompanied by increased Rho activation and MLC phosphorylation and was reversed by inhibition of Rho kinase. Although fibroblasts are known to bind to fibronectin's RGD and synergy sites, their relative contribution to cell function is not clear. MLC phosphorylation was reduced and cell contraction was reversed when FN's synergy site was blocked, indicating that contraction requires signals from the synergy site in addition to TGF-beta-mediated Rho activation. Thus, regulating the FN synergy site therapeutically may provide a mechanism for modulating contractile forces during tissue repair. (c) 2007 Elsevier Inc. All rights reserved.