{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:59:21Z","timestamp":1790513961259,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Activin A (ActA) is considered to play a major role in cancer-induced cachexia (CC). Indeed, circulating ActA levels are elevated and predict survival in patients with CC. However, the mechanisms by which ActA mediates CC development and in particular skeletal muscle (SM) atrophy in humans are not yet fully understood. In this work, we aimed to investigate the effects of ActA on human SM and in mouse models of CC. We used a model of human muscle cells in culture to explore how ActA acts towards human SM. In this model, recombinant ActA induced myotube atrophy associated with the decline of MyHC-\u03b2\/slow, the main myosin isoform in human muscle cells studied. Moreover, ActA inhibited the expression and activity of MEF2C, the transcription factor regulating MYH7, the gene which codes for MyHC-\u03b2\/slow. This decrease in MEF2C was involved in the decline of MyHC-\u03b2\/slow expression, since inhibition of MEF2C by a siRNA leads to the decrease in MyHC-\u03b2\/slow expression. The relevance of this ActA\/MEF2C pathway in vivo was supported by the parallel decline of MEF2C expression and SM mass, which are both blunted by ActA inhibition, in animal models of CC. In this work, we showed that ActA is a potent negative regulator of SM mass by inhibiting MyHC-\u03b2\/slow synthesis through downregulation of MEF2C. This observation highlights a novel interaction between ActA signaling and MEF2C transcriptional activity which contributes to SM atrophy in CC models.<\/jats:p>","DOI":"10.3390\/cells11071119","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T15:31:21Z","timestamp":1648222281000},"page":"1119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Activin A Causes Muscle Atrophy through MEF2C-Dependent Impaired Myogenesis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2887-0721","authenticated-orcid":false,"given":"Audrey","family":"Loumaye","sequence":"first","affiliation":[{"name":"Pole of Endocrinology, Diabetology and Nutrition, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"},{"name":"Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Lause","sequence":"additional","affiliation":[{"name":"Pole of Endocrinology, Diabetology and Nutrition, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indiana University Simon and Bren Comprehensive Cancer Center, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA"},{"name":"Research Service, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-0540","authenticated-orcid":false,"given":"Teresa A.","family":"Zimmers","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indiana University Simon and Bren Comprehensive Cancer Center, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA"},{"name":"Research Service, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3747-3234","authenticated-orcid":false,"given":"Laure B.","family":"Bindels","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Thissen","sequence":"additional","affiliation":[{"name":"Pole of Endocrinology, Diabetology and Nutrition, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"},{"name":"Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1152\/physrev.00002.2018","article-title":"Activin A in Mammalian Physiology","volume":"99","author":"Bloise","year":"2019","journal-title":"Physiol. 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