Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Unit of Dermatology and Venereology, Karolinska University Hospital, Stockholm, Sweden.
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。
