WNT7A suppresses adipogenesis of skeletal muscle mesenchymal stem cells and fatty infiltration through the alternative Wnt-Rho-YAP/TAZ signaling axis

Chengcheng Fu, Britney Chin-Young, Ga Young Park, Mariana Guzmán-Seda, Damien Laudier, Woojin M. Han

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 languageEnglish
Pages (from-to)999-1014
Number of pages16
JournalStem Cell Reports
Volume18
Issue number4
DOIs
StatePublished - 11 Apr 2023

Keywords

  • WNT7a
  • YAP/TAZ
  • adipogenesis
  • fatty infiltration
  • fibro-adipogenic progenitors
  • mesenchymal stem cells
  • skeletal muscle

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