{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:43:50Z","timestamp":1790693030275,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T00:00:00Z","timestamp":1473984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR063786"],"award-info":[{"award-number":["AR063786"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB\u2010activated muscle catabolism is poorly defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the role of p38\u03b2 mitogen\u2010activated protein kinases (MAPK) in mediating ActRIIB ligand activin A\u2010activated muscle catabolic pathways in C2C12 myotubes and in mice with perturbation of this kinase pharmacologically and genetically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment of C2C12 myotubes with activin A or myostatin rapidly activated p38 MAPK and its effector C\/EBP\u03b2 within 1\u2009h. Paradoxically, Akt was activated at the same time through a p38 MAPK\u2010independent mechanism. These events were followed by up\u2010regulation of ubiquitin ligases atrogin1 (MAFbx) and UBR2 (E3\u03b1\u2010II), as well as increase in LC3\u2010II, a marker of autophagosome formation, leading to myofibrillar protein loss and myotube atrophy. The catabolic effects of activin A were abolished by p38\u03b1\/\u03b2 MAPK inhibitor SB202190. Using small interfering RNA\u2010mediated gene knockdown, we found that the catabolic activity of activin A was dependent on p38\u03b2 MAPK specifically. Importantly, systemic administration of activin A to mice similarly activated the catabolic pathways <jats:italic>in vivo<\/jats:italic>, and this effect was blocked by SB202190. Further, activin A failed to activate the catabolic pathways in mice with muscle\u2010specific knockout of p38\u03b2 MAPK. Interestingly, activin A up\u2010regulated MuRF1 in a p38 MAPK\u2010independent manner, and MuRF1 did not appear responsible for activin A\u2010induced myosin heavy chain loss and muscle atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ActRIIB\u2010mediated activation of muscle catabolism is dependent on p38\u03b2 MAPK\u2010activated signalling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12145","type":"journal-article","created":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T11:30:10Z","timestamp":1474025410000},"page":"202-212","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Activin A induces skeletal muscle catabolism via p38\u03b2 mitogen\u2010activated protein kinase"],"prefix":"10.1002","volume":"8","author":[{"given":"Hui","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Pharmacology University of Texas Health Science Center  Houston TX 77030 USA"},{"name":"Department of Respiratory Medicine Yixing Hospital affiliated to Jiangsu University  Yixing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology University of Texas Health Science Center  Houston TX 77030 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Wai Thomas","family":"Sin","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology University of Texas Health Science Center  Houston TX 77030 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhelong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology University of Texas Health Science Center  Houston TX 77030 USA"},{"name":"Division of Endocrinology, Tongji Hospital, Tongji Medical College Huazhong University 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