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=8

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