miR-155 Promotes Cutaneous Wound Healing Through Enhanced Keratinocyte Migration by MMP-2

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  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 in various cancers, however, its function in skin wound healing is largely unknown.Here we hypothesize that miR-155 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 showed 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 showed that MMP-2 was significantly upregulated while 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 promotive 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.
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