HIF-1α Directly Controls WNT7A Expression During Myogenesis.

Herein we unveil that Hypoxia-inducible factor-1α (HIF-1α) directly regulates 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 promoter. Remarkably, a pharmacological activation of HIF-1α induced expression and enhanced muscle differentiation. On the other hand, silencing of using CRISPR/Cas9 genome editing blocked the effects of HIF-1α activation on myogenesis. Finally, treatment with prolyl hydroxylases (PHDs) inhibitors improved muscle regeneration and 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.