Nrf2 regulates skeletal muscle mass and function in a mouse model of experimental autoimmune myositis

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Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders affecting skeletal muscle, which are characterized by loss of muscle mass and function. We have previously demonstrated that experimental autoimmune myositis (EAM) mice, a widely used animal model for IIMs, induced intrinsic contractile dysfunction, which is associated with increased oxidative stress. Here, we investigated the role of Nrf2, the master regulator of antioxidant gene transcription, in muscle mass and function from EAM mice. EAM was induced in muscle-specific Nrf2 knockout (Nrf2 mKO) and wild-type littermates (WT) mice by immunization with three injections of myosin emulsified in complete Freund's adjuvant. At 4 weeks after the first immunization, a grip strength test was performed using a grip strength meter. After that, mice were sacrificed by cervical dislocation under isoflurane anesthesia and harvested oxidative soleus, plantaris, tibialis anterior, gastrocnemius with mixed fiber types, glycolytic extensor digitorum longus, and white vastus lateralis muscles. Nrf2 mKO mice tended to attenuate EAM-induced decrease of muscle force. Nrf2 mKO mice significantly attenuates EAM-induced decrease of muscle weight in the glycolytic extensor digitorum longus, but not in the oxidative muscle. These results suggested that loss of Nrf2 help preserve muscle mass and function in EAM mice, which may be attributed to the mechanisms other than regulation of antioxidant defense by Nrf2.