Yang Longlong, Zheng Zhao, Zhou Qin, Bai Xiaozhi, Fan Lei, Yang Chen, Su Linlin, Hu Dahai
Department of Burn and Plastic Surgery, The First Affiliated Hospital to PLA General Hospital, Beijing, China.
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, Shaanxi, China.
J Mol Histol. 2017 Apr;48(2):147-155. doi: 10.1007/s10735-017-9713-8. Epub 2017 Feb 28.
Inflammation, re-epithelization and tissue remodeling are three essential steps during wound healing. The re-epithelization process plays the most important role which mainly involves keratinocyte proliferation and migration. miR-155 has been reported to participate in cell migration and transformation, however, its function in skin wound healing is largely unknown. Here we hypothesize that overexpression of miR-155 at wound edges could accelerate wound healing mediated by enhanced keratinocyte migration. To test this hypothesis, direct local injection of miR-155 expression plasmid to wound edges was conducted to overexpress miR-155 in vivo. Results shown that miR-155 significantly promoted wound healing and re-epithelization compared to control, while did not affect wound contraction. Also, miR-155 overexpression accelerated primarily cultured keratinocyte migration in vitro, but had no effect on cell proliferation. Importantly, western blot analysis shown that MMP-2 was significantly upregulated whiles its inhibitor TIMP-1 downregulated after miR-155 treatment. Moreover, the use of ARP-101, an MMP-2 inhibitor, effectively attenuated the accelerative effects on cell migration induced by miR-155. Taken together, our results suggest that miR-155 has the promote effect on wound healing that is probably mediated by accelerating keratinocyte migration via upregulated MMP-2 level. This study provides a rationale for the therapeutic effect of miR-155 on wound healing.
炎症、再上皮化和组织重塑是伤口愈合过程中的三个基本步骤。再上皮化过程起着最重要的作用，主要涉及角质形成细胞的增殖和迁移。据报道，miR-155参与细胞迁移和转化，然而，其在皮肤伤口愈合中的功能尚不清楚。在此，我们假设在伤口边缘过表达miR-155可通过增强角质形成细胞迁移来加速伤口愈合。为了验证这一假设，我们将miR-155表达质粒直接局部注射到伤口边缘，以在体内过表达miR-155。结果显示，与对照组相比，miR-155显著促进了伤口愈合和再上皮化，而不影响伤口收缩。此外，miR-155过表达在体外加速了原代培养的角质形成细胞迁移，但对细胞增殖没有影响。重要的是，蛋白质印迹分析显示，miR-155处理后MMP-2显著上调，而其抑制剂TIMP-1下调。此外，使用MMP-2抑制剂ARP-101可有效减弱miR-155诱导的细胞迁移加速作用。综上所述，我们的结果表明，miR-155对伤口愈合具有促进作用，这可能是通过上调MMP-2水平加速角质形成细胞迁移来介导的。本研究为miR-155对伤口愈合的治疗作用提供了理论依据。
