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M-R."],"award-info":[{"award-number":["Empleo juvenil YEI a \u00c1. M-R."]}],"id":[{"id":"10.13039\/501100006541","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008061","name":"Fundaci\u00f3n Mutua Madrile\u00f1a","doi-asserted-by":"publisher","award":["2020"],"award-info":[{"award-number":["2020"]}],"id":[{"id":"10.13039\/100008061","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Senefro","award":["SENEFRO 18\/01"],"award-info":[{"award-number":["SENEFRO 18\/01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis increases glucocorticoid and decreases IGF-1, leading to skeletal muscle wasting and cachexia. Muscle atrophy mainly takes place in locomotor muscles rather than in respiratory ones. Our study aimed to elucidate the mechanism responsible for this difference in muscle proteolysis, focusing on local inflammation and IGF-1 as well as on their glucocorticoid response and HDAC4-myogenin activation. Sepsis was induced in adult male rats by lipopolysaccharide (LPS) injection (10 mg\/kg), and 24 h afterwards, rats were euthanized. LPS increased TNF\u03b1 and IL-10 expression in both muscles studied, the diaphragm and gastrocnemius, whereas IL-6 and SOCS3 mRNA increased only in diaphragm. In comparison with gastrocnemius, diaphragm showed a lower increase in proteolytic marker expression (atrogin-1 and LC3b) and in LC3b protein lipidation after LPS administration. LPS increased the expression of glucocorticoid induced factors, KLF15 and REDD1, and decreased that of IGF-1 in gastrocnemius but not in the diaphragm. In addition, an increase in HDAC4 and myogenin expression was induced by LPS in gastrocnemius, but not in the diaphragm. In conclusion, the lower activation of both glucocorticoid signaling and HDAC4-myogenin pathways by sepsis can be one of the causes of lower sepsis-induced proteolysis in the diaphragm compared to gastrocnemius.<\/jats:p>","DOI":"10.3390\/ijms23073641","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:27:51Z","timestamp":1648416471000},"page":"3641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"\u00c1lvaro","family":"Moreno-Rup\u00e9rez","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5397-0877","authenticated-orcid":false,"given":"Teresa","family":"Priego","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Nursing, Physiotherapy and Podiatry, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3514-4616","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"Gonz\u00e1lez-Nicol\u00e1s","sequence":"additional","affiliation":[{"name":"Renal Physiopathology Laboratory, Department of Nephrology, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-6276","authenticated-orcid":false,"given":"Asunci\u00f3n","family":"L\u00f3pez-Calder\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-679X","authenticated-orcid":false,"given":"Alberto","family":"L\u00e1zaro","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Renal Physiopathology Laboratory, Department of Nephrology, Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4445-590X","authenticated-orcid":false,"given":"Ana Isabel","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00011-016-0937-y","article-title":"Sepsis: In search of cure","volume":"65","author":"Lakshmikanth","year":"2016","journal-title":"Inflamm. 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