Abstract
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.
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Abbreviations
- rhPDGF:
-
Recombinant human platelet derived growth factor
- HDMECs:
-
Human dermal microvascular endothelial cells
- TGF-β:
-
Transforming growth factor beta
- TIMPs:
-
Tissue inhibitors of metalloproteinases
- ECM:
-
Extracellular matrix
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This work was supported by National Natural Science Foundation of China (81601686).
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The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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Longlong Yang and Zhao Zheng have contributed equally to this work.
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Yang, L., Zheng, Z., Zhou, Q. et al. miR-155 promotes cutaneous wound healing through enhanced keratinocytes migration by MMP-2. J Mol Hist 48, 147–155 (2017). https://doi.org/10.1007/s10735-017-9713-8
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DOI: https://doi.org/10.1007/s10735-017-9713-8