{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T22:56:04Z","timestamp":1794264964475,"version":"4.9.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,12,30]],"date-time":"2013-12-30T00:00:00Z","timestamp":1388361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000948","name":"Pfizer Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>\n                    In models of cancer cachexia, inhibiting type IIB activin receptors (ActRIIBs) reverse muscle wasting and prolongs survival, even with continued tumor growth. ActRIIB mediates signaling of numerous TGF\u2010\u03b2 proteins; of these, we demonstrate that activins are the most potent negative regulators of muscle mass. To determine whether activin signaling in the absence of tumor\u2010derived factors induces cachexia, we used recombinant serotype 6 adeno\u2010associated virus (rAAV6) vectors to increase circulating activin A levels in C57BL\/6 mice. While mice injected with control vector gained ~10% of their starting body mass (3.8\u00b10.4 g) over 10 wk, mice injected with increasing doses of rAAV6:activin A exhibited weight loss in a dose\u2010dependent manner, to a maximum of \u201312.4% (\u20134.2\u00b11.1 g). These reductions in body mass in rAAV6:activin\u2010injected mice correlated inversely with elevated serum activin A levels (7\u2010 to 24\u2010fold). Mechanistically, we show that activin A reduces muscle mass and function by stimulating the ActRIIB pathway, leading to deleterious consequences, including increased transcription of atrophy\u2010related ubiquitin ligases, decreased Akt\/mTOR\u2010mediated protein synthesis, and a profibrotic response. Critically, we demonstrate that the muscle wasting and fibrosis that ensues in response to excessive activin levels is fully reversible. These findings highlight the therapeutic potential of targeting activins in cachexia.\u2014Chen, J. L., Walton, K. L., Winbanks, C. E., Murphy, K. T., Thomson, R. E., Makanji, Y., Qian, H., Lynch, G. S., Harrison, C. A., Gregorevic, P. Elevated expression of activins promotes muscle wasting and cachexia.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 28\u20131711 (1723).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-245894","type":"journal-article","created":{"date-parts":[[2013,12,30]],"date-time":"2013-12-30T21:50:58Z","timestamp":1388440258000},"page":"1711-1723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":188,"title":["Elevated expression of activins promotes muscle wasting and cachexia"],"prefix":"10.1096","volume":"28","author":[{"given":"Justin L.","family":"Chen","sequence":"first","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute Melbourne Victoria Australia"},{"name":"Prince Henry's Institute Clayton Victoria 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