{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:17:02Z","timestamp":1792894622367,"version":"4.5.0"},"reference-count":25,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Scientific Research from the Japanese Society for Promotion of Science","award":["21K07339"],"award-info":[{"award-number":["21K07339"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic inflammation causes muscle wasting. Because most inflammatory cytokine signals are mediated via TGF-\u03b2-activated kinase-1 (TAK1) activation, inflammatory cytokine-induced muscle wasting may be ameliorated by the inhibition of TAK1 activity. The present study was undertaken to clarify whether TAK1 inhibition can ameliorate inflammation-induced muscle wasting. SKG\/Jcl mice as an autoimmune arthritis animal model were treated with a small amount of mannan as an adjuvant to enhance the production of TNF-\u03b1 and IL-1\u03b2. The increase in these inflammatory cytokines caused a reduction in muscle mass and strength along with an induction of arthritis in SKG\/Jcl mice. Those changes in muscle fibers were mediated via the phosphorylation of TAK1, which activated the downstream signaling cascade via NF-\u03baB, p38 MAPK, and ERK pathways, resulting in an increase in myostatin expression. Myostatin then reduced the expression of muscle proteins not only via a reduction in MyoD1 expression but also via an enhancement of Atrogin-1 and Murf1 expression. TAK1 inhibitor, LL-Z1640-2, prevented all the cytokine-induced changes in muscle wasting. Thus, TAK1 inhibition can be a new therapeutic target of not only joint destruction but also muscle wasting induced by inflammatory cytokines.<\/jats:p>","DOI":"10.3390\/ijms25115715","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T08:30:22Z","timestamp":1716539422000},"page":"5715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Inflammatory Cytokine-Induced Muscle Atrophy and Weakness Can Be Ameliorated by an Inhibition of TGF-\u03b2-Activated Kinase-1"],"prefix":"10.3390","volume":"25","author":[{"given":"Mai","family":"Kanai","sequence":"first","affiliation":[{"name":"Department of Bioregulatory Sciences, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byambasuren","family":"Ganbaatar","sequence":"additional","affiliation":[{"name":"Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0780-0065","authenticated-orcid":false,"given":"Itsuro","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Bioregulatory Sciences, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiyo","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumpei","family":"Teramachi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"},{"name":"Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8570, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Tenshin","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Higa","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4830-6274","authenticated-orcid":false,"given":"Masahiro","family":"Hiasa","sequence":"additional","affiliation":[{"name":"Department of 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