Li D, Peng H, Qu L, Sommar P, Wang A, Chu T, Li X, Bi X, Liu Q, Sérézal IG, Rollman O, Lohcharoenkal W, Zheng X, Angelstig SE, Grünler J, Pivarcsi A, Sonkoly E, Catrina SB, Xiao C, Ståhle M, Mi QS, Zhou L, and Landén NX. miR-19a/b and miR-20a promote wound healing by regulating the inflammatory response of keratinocytes. J Invest Dermatol 2020.
The Journal of investigative dermatology
Persistent and impaired inflammation impedes tissue healing and is characteristic of chronic wounds. A better understanding of the mechanisms controlling wound inflammation is needed. Here we show that in human wound-edge keratinocytes, the expression of miR-17, miR-18a, miR-19a, miR-19b, and miR-20a, which all belong to the miR-17∼92 cluster, is upregulated during wound repair. However, their levels are lower in chronic ulcers than acute wounds at the proliferative phase. Conditional knockout of miR-17∼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∼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-κB activation by targeting SHCBP1 and SEMA7A, respectively, reducing the production of inflammatory chemokines/cytokines by keratinocytes. Thus, as crucial regulators of wound inflammation, lack of miR-19a/b and miR-20a 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.
ePub ahead of print