Hif2α gene deletion in satellite cells rescues muscle regenerative capacity under hypoxic conditions

Hypoxia, which is the condition where there is reduced oxygen concentration in the air, is a common condition in patients suffering from chronic obstructive pulmonary disease (COPD), peripheral artery diseases (PAD), and for people who live in high altitudes. Individuals under chronic hypoxic conditions suffer from muscle atrophy, a process where muscle homeostasis is disrupted and protein degradation occurs via the E3 ubiquitin proteasomal pathway. Under hypoxia, upregulation of hypoxia inducible factors (HIFs) control the stemness of muscle progenitor cells called satellite cells (SCs). We confirmed the delayed regeneration of tibialis anterior muscle in wildtype mice. Using a conditional gene deletion of Hif2 in Pax7+ SCs, we also observed rescue of muscle regenerative capacity in Hif2 KO mice under hypoxia at 13-14% O2. However, only a decrease in autophagic flux markers but not an increase in muscle atrophy markers in whole muscle could be confirmed.