从αvβ5整合素转换为αvβ6整合素是CD9调节角质形成细胞迁移和MMP-9激活所必需的。
Switch from αvβ5 to αvβ6 integrin is required for CD9-regulated keratinocyte migration and MMP-9 activation.
作者信息
Jiang Xupin, Teng Miao, Guo Xiaowei, Zhang Dongxia, Zhang Qiong, Zhang Jiaping, Huang Yuesheng
机构信息
Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
出版信息
FEBS Lett. 2014 Nov 3;588(21):4044-52. doi: 10.1016/j.febslet.2014.09.027. Epub 2014 Oct 1.
Our previous research found that tetraspanin CD9 is downregulated in migrating epidermis during wound healing, and CD9 downregulation contributes to keratinocyte migration via matrix metalloproteinase-9 (MMP-9) activation. However, little is known about the mechanisms involved in CD9-regulated keratinocyte migration and MMP-9 activation. In this study, we revealed that the expressions of integrin subunits β5 and β6 were regulated by CD9. Furthermore, CD9 silencing triggered the switch from αvβ5 to αvβ6 integrin in HaCaT keratinocytes and CD9 overexpression reversed the switch. Importantly, integrin αvβ6 functional blocking antibody 10D5 significantly inhibited CD9 silencing-induced keratinocyte migration and MMP-9 activation, suggesting that the switch from αvβ5 to αvβ6 integrin plays a key role in CD9-regulated cell migration and MMP-9 activation in keratinocytes.
我们之前的研究发现，在伤口愈合过程中迁移的表皮中四跨膜蛋白CD9表达下调，并且CD9下调通过基质金属蛋白酶-9（MMP-9）激活促进角质形成细胞迁移。然而，关于CD9调节角质形成细胞迁移和MMP-9激活所涉及的机制知之甚少。在本研究中，我们发现整合素亚基β5和β6的表达受CD9调节。此外，CD9沉默触发了HaCaT角质形成细胞中从αvβ5整合素向αvβ6整合素的转变，而CD9过表达则逆转了这种转变。重要的是，整合素αvβ6功能阻断抗体10D5显著抑制CD9沉默诱导的角质形成细胞迁移和MMP-9激活，这表明从αvβ5整合素向αvβ6整合素的转变在CD9调节的角质形成细胞迁移和MMP-9激活中起关键作用。
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