期刊
FASEB JOURNAL
卷 34, 期 9, 页码 12691-12701出版社
WILEY
DOI: 10.1096/fj.202000506R
关键词
adipogenesis; FAP; KLF6; mir-22-3p; muscle injury
资金
- National Natural Science Foundation of China (NSFC) [81672215]
Fibro/adipogenic progenitors (FAPs) are the main cellular source of fatty degeneration in muscle injury; however, the underlying mechanism of FAP adipogenesis in muscle degeneration needs to be further examined. Matrix metalloproteinase 14 (MMP-14) has been reported to induce the adipogenesis of 3T3-L1 preadipocytes, but whether MMP-14 also regulates the differentiation of FAPs remains unclear. To investigate whether and how MMP-14 regulates FAP adipogenesis and fatty infiltration in muscle degeneration, we examined MMP-14 expression in degenerative muscles and tested the effect of MMP-14 on FAP adipogenesis in vitro and in vivo. As expected, MMP-14 enhanced FAP adipogenesis and fatty infiltration in degenerative muscles; moreover, blocking endogenous MMP-14 in injured muscles facilitated muscle repair. Further investigations revealed that Kruppel-like factor 6 (KLF6) was a transcription factor associated with MMP-14 and acted as an on-off switch in the differentiation of FAPs into adipocytes or myofibroblasts. Moreover, KLF6 was the target gene of miR-22-3p, which was downregulated during FAP adipogenesis both in vitro and in vivo, and overexpression of miR-22-3p markedly prevented FAP adipogenesis and attenuated fatty degeneration in muscles. Our study revealed that miR-22-3p/KLF6/MMP-14 is a novel pathway in FAP adipogenesis and that inhibiting KLF6 is a potential strategy for the treatment of muscular degenerative diseases.
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