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.

中文翻译：

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CD9通过将E-钙粘着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。

在角质形成细胞分层和伤口愈合期间，角质形成细胞经历分化和运动性之间的转换。但是，有关切换机制的知识有限。先前我们已经证明CD9的表达在不同的伤口阶段发生了变化，并参与了角质形成细胞迁移的调节。在这项研究中，我们表明CD9表达在经历分化的人和小鼠角质形成细胞中均增加。CD9在角质形成细胞中的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-钙黏着蛋白募集到质膜上，随后激活了PI3K / Akt信号传导，CD9抑制可抑制E-cadherin向质膜的募集和PI3K / Akt的激活。重要的是，沉默E-钙粘着蛋白表达或抑制PI3K / Akt信号转导了CD9过表达诱导的分化和运动减少。这些结果证明CD9充当调节角质形成细胞分化和运动性的重要节点。E-钙粘着蛋白募集到质膜和CD9介导的PI3K / Akt信号通路的激活在这些过程中起重要作用。