Abstract
Intramuscular fatty infiltration in muscle injuries and diseases, caused by aberrant adipogenesis of fibro-adipogenic progenitors, negatively impacts function. Intramuscular delivery of wingless-type MMTV integration site family 7a (WNT7A) offers a promising strategy to stimulate muscle regeneration, but its effects on adipogenic conversion of fibro-adipogenic progenitors remain unknown. Here, we show that WNT7A decreases adipogenesis of fibro-adipogenic progenitors (FAPs) by inducing nuclear localization of Yes-associated protein (YAP) through Rho in a β-CATENIN-independent manner and by promoting nuclear retention of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) in differentiating FAPs. Furthermore, intramuscular injection of WNT7A in vivo effectively suppresses fatty infiltration in mice following glycerol-induced injury. Our results collectively suggest WNT7A as a potential protein-based therapeutic for diminishing adipogenesis of FAPs and intramuscular fatty infiltration in pathological muscle injuries or diseases.
Original language | English |
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Pages (from-to) | 999-1014 |
Number of pages | 16 |
Journal | Stem Cell Reports |
Volume | 18 |
Issue number | 4 |
DOIs | |
State | Published - 11 Apr 2023 |
Keywords
- WNT7a
- YAP/TAZ
- adipogenesis
- fatty infiltration
- fibro-adipogenic progenitors
- mesenchymal stem cells
- skeletal muscle