miRNA-132 通过调节 RAS p21 蛋白激活因子 1 促进皮肤伤口愈合中的成纤维细胞迁移。
MicroRNA-132 promotes fibroblast migration via regulating RAS p21 protein activator 1 in skin wound healing.
机构信息
Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Unit of Dermatology and Venereology, Karolinska University Hospital, Stockholm, Sweden.
出版信息
Sci Rep. 2017 Aug 10;7(1):7797. doi: 10.1038/s41598-017-07513-0.
MicroRNA (miR)-132 has been identified as a top up-regulated miRNA during skin wound healing and its inhibition impairs wound repair. In a human in vivo surgical wound model, we showed that miR-132 was induced in epidermal as well as in dermal wound-edge compartments during healing. Moreover, in a panel of cells isolated from human skin wounds, miR-132 was found highly expressed in human dermal fibroblasts (HDFs). In HDFs, miR-132 expression was upregulated by TGF-β1. By overexpression or inhibition of miR-132, we showed that miR-132 promoted HDF migration. Mechanistically, global transcriptome analysis revealed that RAS signaling pathway was regulated by miR-132 in HDFs. We found that RAS p21 protein activator 1 (RASA1), a known target of miR-132, was downregulated in HDFs upon miR-132 overexpression. Silencing of RASA1 phenocopied the pro-migratory effect of miR-132. Collectively, our study reveals an important role for miR-132 in HDFs during wound healing and indicates a therapeutic potential of miR-132 in hard-to-heal skin wounds.
miR-132 在皮肤伤口愈合过程中被鉴定为上调最显著的 microRNA 之一，其抑制会损害伤口修复。在人类体内手术伤口模型中，我们发现 miR-132 在愈合过程中表皮和真皮伤口边缘区域均被诱导。此外，在从人类皮肤伤口中分离的一系列细胞中，miR-132 在人真皮成纤维细胞 (HDFs) 中高度表达。在 HDFs 中，TGF-β1 上调 miR-132 的表达。通过 miR-132 的过表达或抑制，我们发现 miR-132 促进了 HDF 的迁移。通过机制研究发现，全转录组分析显示 miR-132 在 HDFs 中调节 RAS 信号通路。我们发现，RAS 信号通路 p21 蛋白激活因子 1 (RASA1)，miR-132 的已知靶标，在 miR-132 过表达时在 HDFs 中下调。RASA1 的沉默模拟了 miR-132 的促迁移作用。综上所述，我们的研究揭示了 miR-132 在 HDFs 伤口愈合过程中的重要作用，并表明 miR-132 在难以愈合的皮肤伤口中有治疗潜力。
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