{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:30:44Z","timestamp":1788237044787,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171135"],"award-info":[{"award-number":["32171135"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Hydrogen sulphide (H\n 2<\/jats:sub>\n S), a gasotransmitter synthesized by cystathionine\u2010\u03b3\u2010lyase (CSE), exhibits antioxidant properties and may mimic exercise\u2010induced muscle protection. However, its mechanistic role in muscle atrophy and exercise intervention remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Six\u2010month\u2010old male wild\u2010type (WT) and SESN2 knockout (SESN2\n \u2212\/\u2212<\/jats:sup>\n ) C57BL\/6J mice were subjected to a 2\u2010week hindlimb immobilization, followed by combined resistance and aerobic exercise or pharmacological intervention using the H\n 2<\/jats:sub>\n S donor NaHS (30\u2009\u03bcmol\/kg) or the CSE inhibitor DL\u2010propargylglycine (PAG, 50\u2009mg\/kg). In\u00a0vitro, C\n 2<\/jats:sub>\n C\n 12<\/jats:sub>\n myotubes were treated with H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n and NaHS to assess oxidative stress injury. Muscle mass, cross\u2010sectional area (CSA), collagen deposition and oxidative stress markers were evaluated via histology, Western blot and immunofluorescence.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Compared with the immobilization (IM) group, mice receiving a 2\u2010week combined exercise intervention (IM\u2009+\u2009EX) exhibited significantly increased gastrocnemius muscle mass\/body weight (10.86\u2009\u00b1\u20090.62 vs. 8.56\u2009\u00b1\u20091.61,\n p<\/jats:italic>\n \u2009<\u20090.01), enlarged muscle fibre CSA (1628\u2009\u00b1\u2009265\u2009\u03bcm\n 2<\/jats:sup>\n vs. 905.5\u2009\u00b1\u200988.52\u2009\u03bcm\n 2<\/jats:sup>\n ,\n p<\/jats:italic>\n \u2009<\u20090.01) and reduced collagen deposition as indicated by Sirius red staining (collagen\u2010positive area: 2.86%\u2009\u00b1\u20091.12% vs. 7.06\u2009\u00b1\u20091.18%,\n p<\/jats:italic>\n \u2009<\u20090.001). Pharmacological inhibition of CSE with PAG significantly attenuated these exercise\u2010induced improvements (muscle mass\/body weight: 10.22\u2009\u00b1\u20090.59, CSA: 1139\u2009\u00b1\u200996.21\u2009\u03bcm\n 2<\/jats:sup>\n , collagen area: 5.04\u2009\u00b1\u20090.66%, all\n p<\/jats:italic>\n \u2009<\u20090.05 vs. IM\u2009+\u2009EX). Conversely, administration of the H\n 2<\/jats:sub>\n S donor NaHS mimicked the protective effects of exercise, increasing muscle mass\/body weight (8.94\u2009\u00b1\u20090.51), CSA (1474\u2009\u00b1\u2009176.1\u2009\u03bcm\n 2<\/jats:sup>\n ) and reducing collagen accumulation (collagen area: 3.04\u2009\u00b1\u20090.74%, all\n p<\/jats:italic>\n \u2009<\u20090.05 vs. IM). In\u00a0vitro, NaHS treatment (30\u2009\u03bcM) significantly reversed H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n \u2010induced reductions in myotube diameter (19.16\u2009\u00b1\u20090.91\u2009\u03bcm vs. 15.61\u2009\u00b1\u20090.72\u2009\u03bcm,\n p<\/jats:italic>\n \u2009<\u20090.01) and improved fusion index (46.47\u2009\u00b1\u20091.51% vs. 35.28\u2009\u00b1\u20092.87%,\n p<\/jats:italic>\n \u2009<\u20090.05). Western blot analysis showed that NaHS upregulated SESN2 and Nrf2 expression, as well as downstream antioxidant proteins HO\u20101 and NQO1 (\n p<\/jats:italic>\n \u2009<\u20090.05), whereas SESN2 knockdown blocked these effects and abolished NaHS\u2010mediated protection in myotubes. In SESN2\n \u2212\/\u2212<\/jats:sup>\n mice, NaHS failed to increase muscle mass\/body weight (7.24\u2009\u00b1\u20091.3 vs. WT\u2009+\u2009NaHS 10.12\u2009\u00b1\u20090.38,\n p<\/jats:italic>\n \u2009<\u20090.001), CSA (699.2\u2009\u00b1\u200921.51\u2009\u03bcm\n 2<\/jats:sup>\n vs. WT\u2009+\u2009NaHS 1189\u2009\u00b1\u200993.27\u2009\u03bcm\n 2<\/jats:sup>\n ,\n p<\/jats:italic>\n \u2009<\u20090.001) or antioxidant capacity, confirming the essential role of SESN2 in mediating H\n 2<\/jats:sub>\n S\u2010dependent muscle protection.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n H\n 2<\/jats:sub>\n S protects against disuse\u2010induced muscle atrophy by enhancing antioxidant defences via the SESN2\/Nrf2 signalling pathway. These findings identify H\n 2<\/jats:sub>\n S as a potential exercise\u2010mimetic therapeutic strategy for preserving muscle mass and function.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70083","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T08:50:06Z","timestamp":1759308606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CSE\/H\n 2<\/sub>\n S\/SESN2 Signalling Mediates the Protective Effect of Exercise Against Immobilization\u2010Induced Muscle Atrophy in Mice"],"prefix":"10.1002","volume":"16","author":[{"given":"Xiuru","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, School of Medical Technology Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, School of Medical 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