{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:36:17Z","timestamp":1773048977390,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171173"],"award-info":[{"award-number":["32171173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["SKL2024Y02"],"award-info":[{"award-number":["SKL2024Y02"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["SMFA20A02"],"award-info":[{"award-number":["SMFA20A02"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Laboratory of Space Medicine","award":["32171173"],"award-info":[{"award-number":["32171173"]}]},{"name":"National Key Laboratory of Space Medicine","award":["SKL2024Y02"],"award-info":[{"award-number":["SKL2024Y02"]}]},{"name":"National Key Laboratory of Space Medicine","award":["SMFA20A02"],"award-info":[{"award-number":["SMFA20A02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hemojuvelin (HJV) is a membrane-bound protein prominently expressed in the skeletal muscle, heart, and liver. Despite its established function in iron regulation, the specific role of HJV in muscle physiology and pathophysiology is not well understood. In this study, we explored the involvement of HJV in disuse-induced muscle atrophy and uncovered the potential mechanisms. Hindlimb unloading (HU) resulted in soleus muscle atrophy in wild type (WT) mice, accompanied by a significant decrease in HJV protein expression. The muscle-specific deletion of Hjv (MKO) exacerbated myofiber atrophy, which was associated with an increase in the expression of muscle ubiquitin ligases following HU. Furthermore, the expression of transforming growth factor-\u03b2 type II receptor (T\u03b2RII) and the level of phosphorylated Smad3 (p-Smad3) were elevated after HU, and these effects were exacerbated in MKO mice. The knockdown of T\u03b2RII in the skeletal muscle of MKO mice mitigated myofiber atrophy and reversed the hyperactivation of the T\u03b2RII\/Smad3 pathway induced by HU. Our findings demonstrate that the absence of HJV contributes to the activation of the T\u03b2RII\/Smad3 signaling pathway and, consequently, the onset of myofiber atrophy in response to HU. Given its abundant expression in skeletal muscle, HJV emerges as a potential therapeutic target for muscle atrophy.<\/jats:p>","DOI":"10.3390\/ijms26052016","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T04:46:37Z","timestamp":1740545197000},"page":"2016","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Loss of HJV Aggravates Muscle Atrophy by Promoting the Activation of the T\u03b2RII\/Smad3 Pathway"],"prefix":"10.3390","volume":"26","author":[{"given":"Lu","family":"Wang","sequence":"first","affiliation":[{"name":"National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing 100094, China"},{"name":"Department of Exercise Physiology, Beijing Sport University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuchen","family":"Tao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing 100094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajie","family":"Jia","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing 100094, China"},{"name":"Department of Exercise Physiology, Beijing Sport University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yuan","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing 100094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjiong","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing 100094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-4034","authenticated-orcid":false,"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing 100094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Chen","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Human Factors Engineering, China Astronaut Research and Training Center, Beijing 100094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/978-981-13-1435-3_29","article-title":"Muscle Atrophy: Present and Future","volume":"1088","author":"Cao","year":"2018","journal-title":"Adv. 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