Work

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

Year: 2023

Type: article

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.

Source: Stem Cell Reports

DOI: 10.1016/j.stemcr.2023.03.001

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

Institutions: Icahn School of Medicine at Mount Sinai, Polytechnic University of Puerto Rico

Language: English

Topic: Hippo pathway signaling and YAP/TAZ

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,800