Skeletal muscle plays key roles in metabolic homeostasis. Loss of muscle mass, called muscle atrophy exacerbates disease-associated metabolic perturbations. In this study, we characterized the molecular functions and mechanisms underlying regulation of skeletal muscle atrophy induced by denervation. Denervation significantly increased the expression of heme oxygenase-1 (HO-1) and atrogenes in skeletal muscle. Forkhead box protein O1 (FoxO1) drastically increased in atrophied muscle and selectively stimulated HO-1 gene transcription through direct DNA binding. Lack of HO-1 substantially attenuated muscle atrophy, whereas HO-1 overexpression caused muscle damage in vitro and in vivo. Collectively, HO-1 induced by FoxO1 may cause skeletal muscle atrophy.
Bibliographical noteFunding Information:
We thank Dr. J. Alam (Alton Ochsner Medical Foundation, New Orleans) for providing pHO4.3k-luc vector and Ms. Hyun Jung Kim for helping histological analysis. This work was supported by the Basic research program ( 2012R1A1B3000603 for ESH and 2011-007983 for JOK) of the National Research Foundation funded by Ministry of Education, Science, and Technology.
- Nerve injury