{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:12:08Z","timestamp":1789456328830,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary sarcopenia is an age\u2010associated disorder with progressive and generalised loss of skeletal muscle strength and mass. Skeletal muscle fibrosis is one of the significant pathological manifestations of age\u2010associated sarcopenia. Decorin, a small dermatan\u2013sulfate proteoglycan, participates in extracellular matrix assembly. In numerous studies, the involvement of decorin is not restricted to matrix structural proteins, and it also affects a diverse variety of biological functions like cell growth, adhesion, migration, proliferation and differentiation. Additionally, it modulates the process of inflammation and fibrillogenesis. Based on these preclinical evidences, we hypothesised that decorin may potentially play an important role in skeletal muscles during ageing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Natural ageing mice (Dcn\n                      <jats:sup>+\/+<\/jats:sup>\n                      ), D\u2010galactose (D\u2010gal)\u2013induced Dcn\n                      <jats:sup>+\/+<\/jats:sup>\n                      , Dcn\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice and NOR\u201010 cell models were established. Grip strength and exercise capacity were evaluated, after the mice were sacrificed to collect their gastrocnemius muscles for assessment of atrophy and fibrosis by haematoxylin and eosin staining, qRT\u2010PCR and Western blotting. Co\u2010immunoprecipitation was used to identify the interaction between decorin and integrin \u03b21 (ITGB1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression levels of decorin were reduced at both mRNA and protein levels in muscle during natural ageing in mice (\u221275.3% of mRNA level; \u221229.5% of protein level) and NOR\u201010 cells (\u221278% of protein level).\n                      <jats:italic>si\u2010Dcn<\/jats:italic>\n                      promoted the expression of \u03b1\u2010SMA (+37.2%) and fibronectin (+53.1%), which are related to muscle fibrosis in D\u2010gal\u2013induced NOR\u201010 cells. In addition, in Dcn\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \u2013D\u2010gal mice, which exhibited more aggravated muscle atrophy including smaller grip strength (\u221221.7%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), downregulation of the ratio of gastrocnemius weight (\u22127.3%), fibre size (Gast: \u221215.3%) and increased levels of \u03b1\u2010SMA (+70.2%), MuRF\u20101 (+30.2%), NLRP3(+19.4%) and p21(+27.2%) proteins compared with Dcn\n                      <jats:sup>+\/+<\/jats:sup>\n                      \u2013D\u2010gal mice. In terms of the underlying mechanisms, the Akt\/mTOR signalling pathway was downregulated in Dcn\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \u2013D\u2010gal mice compared with aged Dcn\n                      <jats:sup>+\/+<\/jats:sup>\n                      \u2013D\u2010gal mice (p\u2010S473\u2010Akt\/Akt: \u221238.1%; p\u2010Ser2448\u2010mTOR\/mTOR: \u221228.8%; p\u2010p70S6K\/p70: \u221240.3%; p\u20104E\u2010BP1: \u221242.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Decorin activation enhanced ITGB1 expression (+46.7% vs. NC,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). si\u2010ITGB1 suppressed the expression of p\u2010S473\u2010Akt and p\u2010Ser2448\u2010mTOR in NOR\u201010 cells with Dcn overexpression. The interaction between decorin and ITGB1 was found in skeletal muscle, suggesting that the regulation of decorin on Akt\/mTOR might depend on ITGB1. Notably, decorin deficiency increased the accumulation of p62 (+47.2%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and LC3b (+50.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The comprehensive results show that decorin plays a sarcoprotective role by activating the ITGB1\/Akt\/mTOR pathway and may serve as a potential therapeutic reagent in age\u2010associated sarcopenia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70144","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T02:01:34Z","timestamp":1764986494000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Decorin Deficiency Promotes D\u2010Galactose\u2013Induced Skeletal Muscle Atrophy and Fibrosis by Regulating ITGB1\/Akt\/mTOR Signalling Pathway"],"prefix":"10.1002","volume":"16","author":[{"given":"Xiaoqin","family":"Luo","sequence":"first","affiliation":[{"name":"College of Life Science Liaoning University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxue","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science Liaoning University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Science Liaoning University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruichang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Science Liaoning University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabing","family":"Lian","sequence":"additional","affiliation":[{"name":"College of Life Science Liaoning University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Science Liaoning University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato\u00a0V.","family":"Iozzo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Anatomy and Cell Biology, and Cancer Cell Biology and Signaling Program, Sidney Kimmel Cancer Center Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Science Liaoning University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Spine Disease Research Institute, Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9065-1151","authenticated-orcid":false,"given":"Xiuli","family":"Bi","sequence":"additional","affiliation":[{"name":"College of Life Science Liaoning University  Shenyang China"},{"name":"Key Laboratory for Chronic Diseases Molecular Mechanism Research and Nutritional Intervention of Shenyang  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603\u2010021\u20101665\u20108"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19010032"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2013.11.025"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afq034"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800622RR"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12750"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13659"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1144090"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2019.04.008"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0959\u2010437x(00)00155\u20106"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179319"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010023\u201004696\u20101"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2741\/a344"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109223"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12767"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003419\u2010y"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.04.026"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12395"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044\u20105040\u20101\u20104"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1875471"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.06.123"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12010074"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.659353"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2022.108933"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.18202"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.12.001"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.3.729"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2020.10.001"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175476"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201040978\u2010w"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010024\u201004990\u20106"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4116"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101200"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101680"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00097"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13587"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00234"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15081801"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076408"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201004400\u20105"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.678670"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.189029"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13073"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13326"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1034404"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70144","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:42:14Z","timestamp":1772959334000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jcsm.70144"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70144","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2024-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70144"}}