AUTHOR=Cirillo Federica , Resmini Giulia , Angelino Elia , Ferrara Michele , Tarantino Adriana , Piccoli Marco , Rota Paola , Ghiroldi Andrea , Monasky Michelle M. , Ciconte Giuseppe , Pappone Carlo , Graziani Andrea , Anastasia Luigi 

TITLE=HIF-1α Directly Controls WNT7A Expression During Myogenesis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 8 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.593508

DOI=10.3389/fcell.2020.593508

ISSN=2296-634X

ABSTRACT=Herein we unveil that HIF-1α directly regulates WNT7A expression during myogenesis. In fact, chromatin immunoprecipitation and site-directed mutagenesis experiments revealed two distinct Hypoxia Response Elements (HREs) that are specific HIF-1α binding sites on the WNT7A promoter. Remarkably, a pharmacological activation of HIF-1α induced WNT7A expression and enhanced muscle differentiation. On the other hand, silencing of WNT7A using CRISPR/Cas9 genome editing blocked the effects of HIF-1α activation on myogenesis. Finally, treatment with prolyl hydroxylases inhibitors improved muscle regeneration in vitro and in vivo in a CTX-induced muscle injury mouse model, paving the way for further studies to test its efficacy on acute and chronic muscular pathologies.