Novel role of microRNA 146b-5p for repression of scar formation in skin wounds

A research team led by Professor Yoshikiyo Akasaka of the Department of Pathology, Toho University, Faculty of Medicine, has revealed for the first time that microRNA146b-5p (miR-146b-5p) reduces the scar formation in rat skin wounds. The proportion of skin scars become reduced during the course of healing, but in keloids and hypertrophic scars, the scars almost become enlarged and do not regress. Using an experimental rat model, they have demonstrated that miR-146b-5p treatment reduces fibrosis and scar formation in rat skin wounds. The present findings can uncover the mechanism of inhibited fibrosis in skin wounds and will reveal the interventions to prevent dysfunctions caused by fibrosis in injured organs. The study was published online in the US scientific journal Journal of Investigative Dermatology on December 18, 2021.

Key messages from the study:

miR-146b-5p suppress fibrosis and scar formation via its targeting repression of PDGFRα expression in rat skin wounds.
Inhibited PDGFRα expression in adipose stromal cells by miRNA146b-5p was shown as a new mechanism for suppression of scar formation in skin wounds.
Identifying the role of miR-146b-5p in inhibited scar formation will not only reveal the mechanism of scar formation in skin wounds but also to develop a therapeutic strategy to prevent dysfunction resulting from fibrosis in injured organs, possibly due to inhibiting fibrosis via miR-146b-5p administration.

The research group has previously reported that basic fibroblast growth factor (bFGF) reduces rat skin wound scarring. In the present study, a comprehensive analysis of rat skin fibroblasts treated with bFGF revealed that the identifying miR-146b-5p reduced the size of rat skin wound scars. miR-146b-5p was found to reduce scar size by suppressing the scar fibrosis through its targeting PDGFRαrepression in skin wounds. Moreover, miRNA146b-5p may suppress PDGFRα expression in adipose stromal cells, which will lead to suppression of the scar fibrotic potential of PDGFRα in adipose tissue.
The findings from this study will not only elucidate the mechanism of adipose tissue-mediated scar fibrosis in skin wounds, but also may prevent dysfunction caused by organ fibrosis by suppressing scar fibrosis in damaged organs via miRNA146b-5p administration.

Figure 1.　Attenuation of dermal fibrosis by miRNA146b-5p in skin wounds. The proportion of fibrotic area in miRNA146b-5p mimic-treated wounds was significantly smaller than that in scrambled RNA-treated wounds. In contrast, the proportion of fibrotic area at day 10 in miRNA146b-5p inhibitor-treated wounds was significantly larger than that in scrambled RNA-treated wounds. Y. Akasaka et al. The role for miRNA146b-5p in the attenuation of dermal fibrosis and angiogenesis by targeting PDGFRα in skin wounds. Reprinted with permission from https://doi.org/10.1016/j.jid.2021.11.037.

Journal:
Journal of Investigative Dermatology (Published on-line: December 18, 2021)

Title:
The role for miRNA146b-5p in the attenuation of dermal fibrosis and angiogenesis by targeting PDGFRα in skin wounds

Authors:
Chie Fujisawa, Makoto Hamanoue, Yayoi Kawano, Daiki Murata, Yuri Akishima-Fukasawa, Tetsuya Okaneya, Takeo Minematsu, Hiromi Sanada, Kayo Tsuburaya, Takuma Isshiki, Tetuo Mikami, Takehisa Hanawa, Yoshikiyo Akasaka*　(*Responsible author)

DOI No.
10.1016/j.jid.2021.11.037

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