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首页> 外文期刊>Biology of the cell >Integrin alpha8beta1 regulates adhesion, migration and proliferation of human intestinal crypt cells via a predominant RhoA/ROCK-dependent mechanism.
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Integrin alpha8beta1 regulates adhesion, migration and proliferation of human intestinal crypt cells via a predominant RhoA/ROCK-dependent mechanism.

机译：整联蛋白alpha8beta1通过主要的RhoA / ROCK依赖性机制调节人肠道隐窝细胞的粘附，迁移和增殖。

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摘要

BACKGROUND: Integrins are transmembrane alphabeta heterodimer receptors that function as structural and functional bridges between the cytoskeleton and ECM (extracellular matrix) molecules. The RGD (arginine-glycine-aspartate tripeptide motif)-dependent integrin alpha8beta1 has been shown to be involved in various cell functions in neuronal and mesenchymal-derived cell types. Its role in epithelial cells remains unknown. RESULTS: Integrin alpha8beta1 was found to be expressed in the crypt cell population of the human intestine but was absent from differentiating and mature epithelial cells of the villus. The function of alpha8beta1 in epithelial crypt cells was investigated at the cellular level using normal HIECs (human intestinal epithelial cells). Specific knockdown of alpha8 subunit expression using an shRNA (small-hairpin RNA) approach showed that alpha8beta1 plays important roles in RGD-dependent cell adhesion, migration and proliferation via a RhoA/ROCK (Rho-associated kinase)-dependent mechanism as demonstrated by active RhoA quantification and pharmacological inhibition of ROCK. Moreover, loss of alpha8beta1, through RhoA/ROCK, impairs FA (focal adhesion) complex integrity as demonstrated by faulty vinculin recruitment. CONCLUSIONS: Integrin alpha8beta1 is expressed in epithelial cells. In intestinal crypt cells, alpha8beta1 is closely involved in the regulation of adhesion, migration and cell proliferation via a predominant RhoA/ROCK-dependent mechanism. These results suggest an important role for this integrin in intestinal crypt cell homoeostasis.
机译：背景：整联蛋白是跨膜字母表异二聚体受体，在细胞骨架和ECM（细胞外基质）分子之间起结构和功能桥的作用。 RGD（精氨酸-甘氨酸-天冬氨酸三肽基序）依赖的整合素α8beta1已显示参与神经元和间充质来源的细胞类型的各种细胞功能。它在上皮细胞中的作用仍然未知。结果：发现整联蛋白α8beta1在人肠的隐窝细胞群中表达，但在绒毛的分化和成熟上皮细胞中却没有。使用正常的HIEC（人肠上皮细胞）在细胞水平上研究了alpha8beta1在上皮隐窝细胞中的功能。使用shRNA（小发夹RNA）方法特异性敲低alpha8亚基的表达表明，alpha8beta1通过依赖RhoA / ROCK（Rho相关激酶）的机制在RGD依赖性细胞粘附，迁移和增殖中发挥重要作用， RhoA定量和ROCK的药理抑制作用。此外，通过RhoA / ROCK丢失alpha8beta1会损害FA（局灶性粘附）复合物的完整性，这是由错误的新蛋白募集所证实的。结论：整联蛋白α8β1在上皮细胞中表达。在肠道隐窝细胞中，alpha8beta1通过主要的RhoA / ROCK依赖性机制密切参与粘附，迁移和细胞增殖的调节。这些结果表明该整联蛋白在肠隐窝细胞同源性中具有重要作用。

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