The small G protein Arf6 expressed in keratinocytes by HGF stimulation is a regulator for skin wound healing.
The small G protein Arf6 expressed in keratinocytes by HGF stimulation is a regulator for skin wound healing.
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DOI：
10.1038/srep46649
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发表时间：
2017-04-21
影响因子：
4.6
通讯作者：
Kanaho Y
中科院分区：
文献类型：
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作者：
Miura Y;Ngo Thai Bich V;Furuya M;Hasegawa H;Takahashi S;Katagiri N;Hongu T;Funakoshi Y;Ohbayashi N;Kanaho Y
皮肤伤口愈合过程的早期步骤，受伤皮肤的再上皮化，是由多种生长因子触发的。然而，生长因子触发皮肤伤口愈合的分子机制还不太清楚。在这里，我们证明，肝细胞生长因子（HGF）/c-Met信号诱导的角质形成细胞中的小G蛋白Arf 6 mRNA的表达是必不可少的皮肤伤口愈合。Arf 6 mRNA的表达显着诱导角质形成细胞在受伤的皮肤，这是专门抑制c-Met抑制剂。角质形成细胞特异性Arf 6条件性敲除小鼠的皮肤伤口愈合显著延迟。此外，Arf 6从角质形成细胞中删除显着抑制HGF刺激的细胞迁移和外周膜皱褶的形成，但不影响皮肤形态和角质形成细胞的增殖/分化。这些结果与以下观点一致，即Arf 6通过响应皮肤创伤的HGF/c-Met信号通路在皮肤角质形成细胞中表达，通过调节角质形成细胞的基于膜动力学的运动细胞功能在皮肤创伤愈合中起重要作用。
The earlier step of cutaneous wound healing process, re-epithelialization of the wounded skin, is triggered by a variety of growth factors. However, molecular mechanisms through which growth factors trigger skin wound healing are less understood. Here, we demonstrate that hepatocyte growth factor (HGF)/c-Met signaling-induced expression of the small G protein Arf6 mRNA in keratinocytes is essential for the skin wound healing. Arf6 mRNA expression was dramatically induced in keratinocytes at the wounded skin, which was specifically suppressed by the c-Met inhibitor. Wound healing of the skin was significantly delayed in keratinocyte-specific Arf6 conditional knockout mice. Furthermore, Arf6 deletion from keratinocytes remarkably suppressed HGF-stimulated cell migration and peripheral membrane ruffle formation, but did not affect skin morphology and proliferation/differentiation of keratinocytes. These results are consistent with the notion that Arf6 expressed in skin keratinocytes through the HGF/c-Met signaling pathway in response to skin wounding plays an important role in skin wound healing by regulating membrane dynamics-based motogenic cellular function of keratinocytes.