| First Author | Li D | Year | 2021 |
| Journal | J Invest Dermatol | Volume | 141 |
| Issue | 3 | Pages | 659-671 |
| PubMed ID | 32949564 | Mgi Jnum | J:304394 |
| Mgi Id | MGI:6510439 | Doi | 10.1016/j.jid.2020.06.037 |
| Citation | Li D, et al. (2021) miR-19a/b and miR-20a Promote Wound Healing by Regulating the Inflammatory Response of Keratinocytes. J Invest Dermatol 141(3):659-671 |
| abstractText | Persistent and impaired inflammation impedes tissue healing and is a characteristic of chronic wounds. A better understanding of the mechanisms controlling wound inflammation is needed. In this study, we show that in human wound-edge keratinocytes, the expressions of microRNA (miR)-17, miR-18a, miR-19a, miR-19b, and miR-20a, which all belong to the miR-17 approximately 92 cluster, are upregulated during wound repair. However, their levels are lower in chronic ulcers than in acute wounds at the proliferative phase. Conditional knockout of miR-17 approximately 92 in keratinocytes as well as injection of miR-19a/b and miR-20a antisense inhibitors into wound edges enhanced inflammation and delayed wound closure in mice. In contrast, conditional overexpression of the miR-17 approximately 92 cluster or miR-19b alone in mice keratinocytes accelerated wound closure in vivo. Mechanistically, miR-19a/b and miR-20a decreased TLR3-mediated NF-kappaB activation by targeting SHCBP1 and SEMA7A, respectively, reducing the production of inflammatory chemokines and cytokines by keratinocytes. Thus, miR-19a/b and miR-20a being crucial regulators of wound inflammation, the lack thereof may contribute to sustained inflammation and impaired healing in chronic wounds. In line with this, we show that a combinatory treatment with miR-19b and miR-20a improved wound healing in a mouse model of type 2 diabetes. |
