ARG-GLY-ASP-CONTAINING PEPTIDES EXPOSE NOVEL COLLAGEN RECEPTORS ON FIBROBLASTS - IMPLICATIONS FOR WOUND-HEALING
ARG-GLY-ASP-CONTAINING PEPTIDES EXPOSE NOVEL COLLAGEN RECEPTORS ON FIBROBLASTS - IMPLICATIONS FOR WOUND-HEALING
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DOI：
10.1091/mbc.2.12.1035
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发表时间：
1991-12-01
期刊：
影响因子：
--
通讯作者：
BURNS, GF
中科院分区：
文献类型：
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作者：
AGREZ, MV;BATES, RC;BURNS, GF
整合素是一个细胞表面受体家族，密切参与细胞与细胞外基质的相互作用。这些受体由非共价结合的α和β亚基组成，许多受体被证明识别和结合其特定细胞外基质配体中包含的精氨酸-甘氨酸-天冬氨酸(RGD)序列。成纤维细胞表达整合素受体，属于两个主要的亚家族。由β-1(VLA)定义的亚家族中的一些成员是胶原的受体，但可能令人惊讶的是，成纤维细胞上的另一个主要的整合素亚家族-由玻璃体连接蛋白受体的阿尔法链定义，α-v-似乎都主要与玻璃体连接蛋白和/或纤维连接蛋白结合。在目前的研究中，我们发现含有RGD的多肽暴露了α-v相关整合素上的隐蔽结合部位，使它们能够作为胶原受体发挥作用。在以I型胶原为基质的成纤维细胞中加入含RGD的多肽可引起细胞显著伸长，当细胞包含在胶原基质中时，多肽可引起凝胶的显著收缩。这些过程被抗α-v-整合素的单抗的Fab片段所抑制。此外，细胞裂解产物中的α-v相关整合素在含有RGD的多肽存在的情况下结合到I型胶原亲和柱上，但不存在。这些数据提示了整合素功能的一种新的调控机制。此外，由于隐蔽的胶原受体被证明与胶原凝胶的收缩有关，这种结合力的产生表明这可能是这些整合素在伤口愈合等过程中的主要生物学作用。
Integrins are a family of cell-surface receptors intimately involved in the interactions of cells with their extracellular matrix. These receptors comprise an alpha and beta-subunit in noncovalent association and many have been shown to recognize and bind an arginine-glycine-aspartate (RGD) sequence contained within their specific extracellular matrix ligand. Fibroblasts express integrin receptors belonging to two major subfamilies. Some of the members within the subfamily defined by beta-1 (VLA) are receptors for collagen but, perhaps surprisingly, the other major subfamily of integrins on fibroblasts-that defined by the alpha-chain of the vitronectin receptor, alpha-v-all appear to bind primarily vitronectin and/or fibronectin. In the present study we show that RGD-containing peptides expose cryptic binding sites on the alpha-v-associated integrins enabling them to function as collagen receptors. The addition of RGD-containing peptides to fibroblasts cultured on type I collagen induced dramatic cell elongation and, when the cells were contained within collagen matrices, the peptides induced marked contraction of the gels. These processes were inhibited by Fab fragments of a monoclonal antibody against an alpha-v-integrin. Also, alpha-v-associated integrins from cell lysates bound to collagen I affinity columns in the presence, but not in the absence, of RGD-containing peptides. These data suggest a novel regulatory control for integrin function. In addition, because the cryptic collagen receptors were shown to be implicated in the contraction of collagen gels, the generation of such binding forces suggests that this may be the major biological role for these integrins in processes such as wound healing.