mir-22-3p/KLF6/MMP14 axis in fibro-adipogenic progenitors regulates fatty infiltration in muscle degeneration.
FASEB J
; 34(9): 12691-12701, 2020 09.
Article
in En
| MEDLINE
| ID: mdl-33000497
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stem Cells
/
MicroRNAs
/
Adipogenesis
/
Matrix Metalloproteinase 14
/
Kruppel-Like Factor 6
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Muscular Diseases
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
China