Vitamin D alleviates dexamethasone-induced skeletal muscle atrophy by regulating the LKB1/AMPK/ACC signaling pathway
Objective To investigate the molecular mechanism by which Vitamin D alleviates dexametha-sone-induced skeletal muscle atrophy by regulating the LKB1/AMPK/ACC signaling pathway.Methods An in vitro myotubular atrophy model was constructed by C2C12-induced differentiation and dexamethasone co-incubation;An in vivo skeletal muscle atrophy model was constructed by intraperitoneal injection of dexamethasone into mice;In vi-tro myotubular diameter,myotubular length and myotubular fusion index were examined by immunofluorescence tech-nique;p-LKB1,p-AMPK,p-ACC,p-AMPK,p-ACC and p-AMPK were examined by immunob1otting in the in vivo and in vitro models.The expression levels of p-LKB1,p-AMPK,p-ACC,Atrogin 1 and other proteins were investi-gated by immunoblotting;the effect of Vitamin D on skeletal muscle strength in mice was examined by mouse grasp strength test;the cross-sectional area of skeletal muscle fibres in mice was examined by HE staining.Results Com-pared with the control group,dexamethasone induction significantly reduced myotube diameter,myotube length,myotube fusion index and mouse grip strength in vivo and in vitro model,significantly increased the expression levels of Atrogin1,MuRF1 and Myostatin,and significantly inhibited the activity of LKB1/AMPK/ACC signaling pathway(P＜0.01);Compared with the dexamethasone treated group,Vitamin D-treated group significantly improved dexa-methasone-induced skeletal muscle atrophy in an ex vivo model in a dose-dependent manner(P＜0.01).Conclusion Vitamin D alleviates dexamethasone-induced skeletal muscle atrophy by regulating the LKB1/AMPK/ACC signaling pathway.
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