CD9 regulates keratinocyte differentiation and motility by recruiting E-cadherin to the plasma membrane and activating the PI3K/Akt pathway
CD9 regulates keratinocyte differentiation and motility by recruiting E-cadherin to the plasma membrane and activating the PI3K/Akt pathway
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CD9 通过将 E-钙粘蛋白募集到质膜并激活 PI3K/Akt 通路来调节角质形成细胞的分化和运动
DOI：
10.1016/j.bbamcr.2019.118574
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发表时间：
2020-02-01
影响因子：
5.1
通讯作者：
Huang, Yuesheng
中科院分区：
文献类型：
--
作者：
Jiang, Xupin;Teng, Miao;Huang, Yuesheng
在角质形成细胞分层和伤口愈合过程中，角质形成细胞经历分化和运动之间的转换。然而，人们对开关机制的了解有限。我们之前已经证明CD9的表达在不同的伤口阶段发生变化并参与角质形成细胞迁移的调节。在这项研究中，我们发现人类和小鼠角质形成细胞在分化过程中 CD9 表达均增加。角质形成细胞中 CD9 过度表达刺激终末分化并降低细胞运动性。 CD9 沉默抑制钙诱导的角质形成细胞分化并增加细胞运动性。此外，CD9 过表达将 E-钙粘蛋白招募到质膜，随后激活 PI3K/Akt 信号传导，而 CD9 敲低则抑制 E-钙粘蛋白向质膜的募集和 PI3K/Akt 激活。重要的是，沉默 E-钙粘蛋白表达或抑制 PI3K/Akt 信号传导可逆转 CD9 过表达诱导的分化和运动性降低。这些结果表明CD9作为调节角质形成细胞分化和运动的重要节点。 E-钙粘蛋白向质膜的募集以及 CD9 介导的 PI3K/Akt 信号通路的激活在这些过程中发挥着重要作用。
During keratinocyte stratification and wound healing, keratinocytes undergo a switch between differentiation and motility. However, limited knowledge exists on the mechanisms of the switch. We have previously demonstrated that the expression of CD9 was changed in different wound stages and involved in the regulation of keratinocyte migration. In this study, we showed that CD9 expression was increased in both human and mouse keratinocytes undergoing differentiation. CD9 overexpression in keratinocytes stimulated terminal differentiation and reduced cell motility. CD9 silencing inhibited calcium-induced keratinocyte differentiation and increased cell motility. Furthermore, CD9 overexpression recruited E-cadherin to the plasma membrane and subsequently activated PI3K/Akt signaling, while CD9 knockdown inhibited the recruitment of E-cadherin to the plasma membrane and PI3K/Akt activation. Importantly, silencing E-cadherin expression or inhibiting PI3K/Akt signaling reversed CD9 overexpression-induced differentiation and-reduced motility. These results demonstrate that CD9 acts as an important node that regulates keratinocyte differentiation and motility. The recruitment of E-cadherin to the plasma membrane and activation of the PI3K/Akt signaling pathway mediated by CD9 play an important role in these processes.