title: TRAF6 inhibition rescues dexamethasone-induced muscle atrophy.
abstract: Tumor necrosis factor receptor-associated factor 6 (TRAF6), a unique E3 ubiquitin ligase and adaptor protein, is involved in activation of various signaling cascades. Recent studies identify TRAF6 as one of the novel regulators of skeletal muscle atrophy. The role of TRAF6 in glucocorticoid-induced muscle atrophy, however, remains to be elucidated. In this study, we show that TRAF6 and its downstream signaling molecules, muscle atrophy F-box (MAFBx) and muscle ring finger 1 (MuRF1), were all upregulated in dexamethasone-induced atrophy of mouse C2C12 myotubes or mouse tibialis anterior (TA) muscle. To further investigate the role of TRAF6 in dexamethasone-induced muscle atrophy, TRAF6-siRNA was used to transfect cultured C2C12 myotubes or was injected into the TA muscle of mice respectively, and we note that TRAF6 knockdown attenuated dexamethasone-induced muscle atrophy in vitro and in vivo, and concomitantly decreased the expression of MuRF1 and MAFBx. Our findings suggest that a decreased expression of TRAF6 could rescue dexamethasone-induced skeletal muscle atrophy through, at least in part, regulation of the expression of MAFBx and MuRF1.
authors: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu, China. sunhl@ntu.edu.cn.
authors: Hualin
authors: H
authors: Sun
authors: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu, China. ntgongyp@sohu.com.
authors: Yanpei
authors: Y
authors: Gong
authors: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu, China. scudlcms@163.com.
authors: Jiaying
authors: J
authors: Qiu
authors: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu, China. chenq_js@163.com.
authors: Yanfei
authors: Y
authors: Chen
authors: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu, China. dingfei@ntu.edu.cn.
authors: Fei
authors: F
authors: Ding
authors: Jiangsu Key Laboratory of Neuroregeneration, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu, China. drzhaoqing@126.com.
authors: Qing
authors: Q
authors: Zhao
mesh_terms: D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000633:toxicity; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism; D009133:Muscular Atrophy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism / Q000627:therapeutic use; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D048029:TNF Receptor-Associated Factor 6; D000070584:Tripartite Motif Proteins; D003907:Dexamethasone; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases