{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:48:57Z","timestamp":1783644537860,"version":"3.55.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011692","name":"General Insurance Association of Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011692","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Keio Orthopaedic Hosoya Foundation","award":["012"],"award-info":[{"award-number":["012"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K09309"],"award-info":[{"award-number":["21K09309"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K08686"],"award-info":[{"award-number":["23K08686"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Skeletal Muscle"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The regenerative and adaptive capacity of skeletal muscles reduces with age, leading to severe disability and frailty in the elderly. Therefore, development of effective therapeutic interventions for muscle wasting is important both medically and socioeconomically. In the present study, we aimed to elucidate the potential contribution of fibro-adipogenic progenitors (FAPs), which are mesenchymal stem cells in skeletal muscles, to immobilization-induced muscle atrophy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Young (2\u20133\u00a0months), adult (12\u201314\u00a0months), and aged (20\u201322\u00a0months) mice were used for analysis. Muscle atrophy was induced by immobilizing the hind limbs with a steel wire. FAPs were isolated from the hind limbs on days 0, 3, and 14 after immobilization for transcriptome analysis. The expression of ST2 and IL-33 in FAPs was evaluated by flow cytometry and immunostaining, respectively. To examine the role of IL-33-ST2 signaling in <jats:italic>vivo<\/jats:italic>, we intraperitoneally administered recombinant IL-33 or soluble ST2 (sST2) twice a week throughout the 2-week immobilization period. After 2-week immobilization, the tibialis anterior muscles were harvested and the cross-sectional area of muscle fibers was evaluated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The number of FAPs increased with the progression of muscle atrophy after immobilization in all age-groups. Transcriptome analysis of FAPs collected before and after immobilization revealed that <jats:italic>Il33<\/jats:italic> and <jats:italic>Il1rl1<\/jats:italic> transcripts, which encode the IL-33 receptor ST2, were transiently induced in young mice and, to a lesser extent, in aged mice. The number of FAPs positive for ST2 increased after immobilization in young mice. The number of ST2-positive FAPs also increased after immobilization in aged mice, but the difference from the baseline was not statistically significant. Immunostaining for IL-33 in the muscle sections revealed a significant increase in the number of FAPs expressing IL-33 after immobilization. Administration of recombinant IL-33 suppressed immobilization-induced muscle atrophy in aged mice but not in young mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our data reveal a previously unknown protective role of IL-33-ST2 signaling against immobilization-induced muscle atrophy in FAPs and suggest that IL-33-ST2 signaling is a potential new therapeutic target for alleviating disuse muscle atrophy, particularly in older adults.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13395-024-00338-2","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T11:01:43Z","timestamp":1711969303000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["IL-33-ST2 signaling in fibro-adipogenic progenitors alleviates immobilization-induced muscle atrophy in mice"],"prefix":"10.1186","volume":"14","author":[{"given":"Yoshiyuki","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Yoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osahiko","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Horiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"338_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186128","volume":"12","author":"L Ma","year":"2017","unstructured":"Ma L, Chu W, Chai J, Shen C, Li D, Wang X. ER stress and subsequent activated calpain play a pivotal role in skeletal muscle wasting after severe burn injury. PLoS ONE. 2017;12: e0186128.","journal-title":"PLoS ONE"},{"key":"338_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101185","volume":"64","author":"CSL Tuttle","year":"2020","unstructured":"Tuttle CSL, Thang LAN, Maier AB. Markers of inflammation and their association with muscle strength and mass: A systematic review and meta-analysis. Ageing Res Rev. 2020;64: 101185.","journal-title":"Ageing Res Rev"},{"key":"338_CR3","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/jcsm.12043","volume":"6","author":"TS Bowen","year":"2015","unstructured":"Bowen TS, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J Cachexia Sarcopenia Muscle. 2015;6:197\u2013207.","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"338_CR4","doi-asserted-by":"publisher","first-page":"3789","DOI":"10.1113\/jphysiol.2013.257121","volume":"591","author":"C Suetta","year":"2013","unstructured":"Suetta C, Frandsen U, Mackey AL, Jensen L, Hvid LG, Bayer ML, et al. Ageing is associated with diminished muscle re-growth and myogenic precursor cell expansion early after immobility-induced atrophy in human skeletal muscle. J Physiol. 2013;591:3789\u2013804.","journal-title":"J Physiol"},{"key":"338_CR5","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1113\/JP274772","volume":"596","author":"E Rejc","year":"2018","unstructured":"Rejc E, Floreani M, Taboga P, Botter A, Toniolo L, Cancellara L, et al. Loss of maximal explosive power of lower limbs after 2 weeks of disuse and incomplete recovery after retraining in older adults. J Physiol. 2018;596:647\u201365.","journal-title":"J Physiol"},{"key":"338_CR6","doi-asserted-by":"publisher","first-page":"C1068","DOI":"10.1152\/ajpcell.00425.2021","volume":"322","author":"EA Nunes","year":"2022","unstructured":"Nunes EA, Stokes T, McKendry J, Currier BS, Phillips SM. Disuse-induced skeletal muscle atrophy in disease and nondisease states in humans: mechanisms, prevention, and recovery strategies. Am J Physiol Cell Physiol. 2022;322:C1068\u201384.","journal-title":"Am J Physiol Cell Physiol"},{"key":"338_CR7","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.phrs.2015.05.010","volume":"99","author":"V Dutt","year":"2015","unstructured":"Dutt V, Gupta S, Dabur R, Injeti E, Mittal A. Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action. Pharmacological Res. 2015;99:86\u2013100.","journal-title":"Pharmacological Res"},{"key":"338_CR8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1152\/physrev.00043.2011","volume":"93","author":"H Yin","year":"2013","unstructured":"Yin H, Price F, Rudnicki MA. Satellite Cells and the Muscle Stem Cell Niche. Physiol Rev. 2013;93:23\u201367.","journal-title":"Physiol Rev"},{"key":"338_CR9","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1038\/s41467-022-30619-7","volume":"13","author":"JG Boyer","year":"2022","unstructured":"Boyer JG, Huo J, Han S, Havens JR, Prasad V, Lin BL, et al. Depletion of skeletal muscle satellite cells attenuates pathology in muscular dystrophy. Nat Commun. 2022;13:2940.","journal-title":"Nat Commun"},{"key":"338_CR10","doi-asserted-by":"publisher","first-page":"3657","DOI":"10.1242\/dev.068858","volume":"138","author":"JJ McCarthy","year":"2011","unstructured":"McCarthy JJ, Mula J, Miyazaki M, Erfani R, Garrison K, Farooqui AB, et al. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle. Development. 2011;138:3657\u201366.","journal-title":"Development"},{"key":"338_CR11","doi-asserted-by":"publisher","first-page":"28456","DOI":"10.1074\/jbc.M115.653477","volume":"290","author":"S Mizuno","year":"2015","unstructured":"Mizuno S, Yoda M, Shimoda M, Tohmonda T, Okada Y, Toyama Y, et al. A Disintegrin and Metalloprotease 10 (ADAM10) Is Indispensable for Maintenance of the Muscle Satellite Cell Pool*. J Biol Chem. 2015;290:28456\u201364.","journal-title":"J Biol Chem"},{"key":"338_CR12","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1016\/j.celrep.2019.04.074","volume":"27","author":"MN Wosczyna","year":"2019","unstructured":"Wosczyna MN, Konishi CT, Perez Carbajal EE, Wang TT, Walsh RA, Gan Q, et al. Mesenchymal Stromal Cells Are Required for Regeneration and Homeostatic Maintenance of Skeletal Muscle. Cell Rep. 2019;27:2029-2035.e5.","journal-title":"Cell Rep"},{"key":"338_CR13","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.scr.2016.06.007","volume":"17","author":"D Fiore","year":"2016","unstructured":"Fiore D, Judson RN, Low M, Lee S, Zhang E, Hopkins C, et al. Pharmacological blockage of fibro\/adipogenic progenitor expansion and suppression of regenerative fibrogenesis is associated with impaired skeletal muscle regeneration. Stem Cell Res. 2016;17:161\u20139.","journal-title":"Stem Cell Res"},{"key":"338_CR14","doi-asserted-by":"publisher","first-page":"e139617","DOI":"10.1172\/JCI139617","volume":"131","author":"A Uezumi","year":"2021","unstructured":"Uezumi A, Ikemoto-Uezumi M, Zhou H, Kurosawa T, Yoshimoto Y, Nakatani M, et al. Mesenchymal Bmp3b expression maintains skeletal muscle integrity and decreases in age-related sarcopenia. J Clin Invest. 2021;131:e139617.","journal-title":"J Clin Invest"},{"key":"338_CR15","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1002\/mus.25202","volume":"54","author":"A Onda","year":"2016","unstructured":"Onda A, Kono H, Jiao Q, Akimoto T, Miyamoto T, Sawada Y, et al. New mouse model of skeletal muscle atrophy using spiral wire immobilization. Muscle Nerve. 2016;54:788\u201391.","journal-title":"Muscle Nerve"},{"key":"338_CR16","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/978-1-4939-3810-0_17","volume":"1460","author":"A Uezumi","year":"2016","unstructured":"Uezumi A, Kasai T, Tsuchida K. Identification, Isolation, and Characterization of Mesenchymal Progenitors in Mouse and Human Skeletal Muscle. Methods Mol Biol. 2016;1460:241\u201353.","journal-title":"Methods Mol Biol"},{"key":"338_CR17","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.yexcr.2004.02.018","volume":"296","author":"S Fukada","year":"2004","unstructured":"Fukada S, Higuchi S, Segawa M, Koda K, Yamamoto Y, Tsujikawa K, et al. Purification and cell-surface marker characterization of quiescent satellite cells from murine skeletal muscle by a novel monoclonal antibody. Exp Cell Res. 2004;296:245\u201355.","journal-title":"Exp Cell Res"},{"key":"338_CR18","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.stem.2018.12.014","volume":"24","author":"L Lukjanenko","year":"2019","unstructured":"Lukjanenko L, Karaz S, Stuelsatz P, Gurriaran-Rodriguez U, Michaud J, Dammone G, et al. Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors. Cell Stem Cell. 2019;24:433-446.e7.","journal-title":"Cell Stem Cell"},{"key":"338_CR19","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/nrd2660","volume":"7","author":"R Kakkar","year":"2008","unstructured":"Kakkar R, Lee RT. The IL-33\/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov. 2008;7:827\u201340.","journal-title":"Nat Rev Drug Discov"},{"key":"338_CR20","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/ncb2015","volume":"12","author":"AWB Joe","year":"2010","unstructured":"Joe AWB, Yi L, Natarajan A, Le Grand F, So L, Wang J, et al. Muscle injury activates resident fibro\/adipogenic progenitors that facilitate myogenesis. Nature Cell Biol. 2010;12:153\u201363.","journal-title":"Nature Cell Biol"},{"key":"338_CR21","doi-asserted-by":"publisher","first-page":"3654","DOI":"10.1242\/jcs.086629","volume":"124","author":"A Uezumi","year":"2011","unstructured":"Uezumi A, Ito T, Morikawa D, Shimizu N, Yoneda T, Segawa M, et al. Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. J Cell Sci. 2011;124:3654\u201364.","journal-title":"J Cell Sci"},{"key":"338_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056641","volume":"8","author":"T Oishi","year":"2013","unstructured":"Oishi T, Uezumi A, Kanaji A, Yamamoto N, Yamaguchi A, Yamada H, et al. Osteogenic Differentiation Capacity of Human Skeletal Muscle-Derived Progenitor Cells. PLoS ONE. 2013;8: e56641.","journal-title":"PLoS ONE"},{"key":"338_CR23","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/s41556-018-0151-y","volume":"20","author":"L Madaro","year":"2018","unstructured":"Madaro L, Passafaro M, Sala D, Etxaniz U, Lugarini F, Proietti D, et al. Denervation-activated STAT3\u2013IL-6 signalling in fibro-adipogenic progenitors promotes myofibres atrophy and fibrosis. Nat Cell Biol. 2018;20:917\u201327.","journal-title":"Nat Cell Biol"},{"key":"338_CR24","doi-asserted-by":"publisher","first-page":"790437","DOI":"10.3389\/fcell.2021.790437","volume":"9","author":"E Parker","year":"2022","unstructured":"Parker E, Khayrullin A, Kent A, Mendhe B, Youssef El Baradie KB, Yu K, et al. Hindlimb Immobilization Increases IL-1\u03b2 and Cdkn2a Expression in Skeletal Muscle Fibro-Adipogenic Progenitor Cells: A Link Between Senescence and Muscle Disuse Atrophy. Front Cell Dev Biol. 2022;9:790437.","journal-title":"Front Cell Dev Biol"},{"key":"338_CR25","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nri.2016.95","volume":"16","author":"FY Liew","year":"2016","unstructured":"Liew FY, Girard J-P, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol. 2016;16:676\u201389.","journal-title":"Nat Rev Immunol"},{"key":"338_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108997","volume":"35","author":"JM Kastenschmidt","year":"2021","unstructured":"Kastenschmidt JM, Coulis G, Farahat PK, Pham P, Rios R, Cristal TT, et al. A stromal progenitor and ILC2 niche promotes muscle eosinophilia and fibrosis-associated gene expression. Cell Rep. 2021;35: 108997.","journal-title":"Cell Rep"},{"key":"338_CR27","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.immuni.2016.01.009","volume":"44","author":"W Kuswanto","year":"2016","unstructured":"Kuswanto W, Burzyn D, Panduro M, Wang KK, Jang YC, Wagers AJ, et al. Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells. Immunity. 2016;44:355\u201367.","journal-title":"Immunity"},{"key":"338_CR28","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1113\/expphysiol.2011.063321","volume":"98","author":"RW Jackman","year":"2013","unstructured":"Jackman RW, Cornwell EW, Wu C-L, Kandarian SC. Nuclear factor-\u03baB signalling and transcriptional regulation in skeletal muscle atrophy. Exp Physiol. 2013;98:19\u201324.","journal-title":"Exp Physiol"},{"key":"338_CR29","doi-asserted-by":"publisher","first-page":"5479","DOI":"10.1074\/jbc.M109.075606","volume":"285","author":"JM Dahlman","year":"2010","unstructured":"Dahlman JM, Bakkar N, He W, Guttridge DC. NF-kappaB functions in stromal fibroblasts to regulate early postnatal muscle development. J Biol Chem. 2010;285:5479\u201387.","journal-title":"J Biol Chem"},{"key":"338_CR30","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.yjmcc.2006.07.006","volume":"41","author":"G Hall","year":"2006","unstructured":"Hall G, Hasday JD, Rogers TB. Regulating the regulator: NF-\u03baB signaling in heart. J Mol Cell Cardiol. 2006;41:580\u201391.","journal-title":"J Mol Cell Cardiol"}],"container-title":["Skeletal Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13395-024-00338-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13395-024-00338-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13395-024-00338-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T11:09:33Z","timestamp":1711969773000},"score":1,"resource":{"primary":{"URL":"https:\/\/skeletalmusclejournal.biomedcentral.com\/articles\/10.1186\/s13395-024-00338-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["338"],"URL":"https:\/\/doi.org\/10.1186\/s13395-024-00338-2","relation":{},"ISSN":["2044-5040"],"issn-type":[{"value":"2044-5040","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,1]]},"assertion":[{"value":"2 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal experiments were approved by the Institutional Animal Care and Use Committee of Keio University School of Medicine (approval #A2021-004).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6"}}