{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:46:55Z","timestamp":1791823615876,"version":"4.3.4"},"reference-count":30,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"abstract":"<jats:p>Introduction: Sarcopenia is a prevalent complication of chronic kidney disease (CKD), yet reliable biomarkers remain limited. CCN1, a matricellular protein involved in cellular senescence, has been implicated in muscle wasting, but its role in CKD-associated muscle strength decline is incompletely understood. Methods: Serum CCN1 levels were measured by ELISA in 40 stage 3\u20135 CKD patients and 27 age-matched controls and correlated with handgrip strength (HGS). A 5\/6 nephrectomy (NX) mouse model was established to evaluate muscle strength and senescence markers. C2C12 myotubes were treated with recombinant CCN1 or Wnt3a, with or without integrin \u03b21 inhibitor or DKK-1. Senescence-associated \u03b2-galactosidase staining, qPCR, Western blot, co-immunoprecipitation, and immunofluorescence were performed to explore mechanisms. Results: GEO database analysis and our clinical data showed significantly elevated serum CCN1 levels in CKD patients versus controls. A trend toward a negative association was observed between serum CCN1 levels and HGS. In NX mice, reduced grip strength was associated with increased skeletal muscle CCN1 expression, upregulation of p53\/p21\/p16, and elevated Fbx32\/Trim63. Co-immunoprecipitation revealed physical interaction between CCN1 and integrin \u03b16\/\u03b21. Blockade of integrin \u03b21 attenuated CCN1-induced myotube senescence. Wnt3a dose-dependently upregulated CCN1 and senescence markers, while DKK-1 partially reversed these effects. Serum from CKD mice with muscle wasting directly induced senescence in C2C12 myotubes, an effect also mitigated by DKK-1. Conclusions: CCN1 promotes muscle senescence through integrin \u03b16\/\u03b21 signaling, with Wnt3a as an upstream regulator. CCN1 may serve as a potential biomarker for CKD-related muscle wasting, and targeting the Wnt3a-CCN1-integrin axis could represent a novel therapeutic strategy.<\/jats:p>","DOI":"10.1159\/000553578","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:00:35Z","timestamp":1787328035000},"page":"1-19","source":"Crossref","is-referenced-by-count":0,"title":["The Regulation of CCN1 Contributes to Skeletal Muscle Wasting in Chronic Kidney Disease"],"prefix":"10.1159","author":[{"given":"Yidan","family":"Zuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2021.11.003"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-8871-2_1"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1177\/2048004016677687"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-012-0078-2"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00066.2013"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2021.100059"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46012"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-019-00534-6"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203882"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfad076"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13112"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.01.416"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2019.12.012"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1080\/0886022X.2019.1627220"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014020144"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2019.111124"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-016-0324-z"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.07.003"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035754"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2007.09.005"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.8.2955-2964.2006"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2018.12.005"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.10261013"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2019.03.005"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2019.10.027"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25105117"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204600"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092115"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2070"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100201"}],"container-title":["American Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000553578","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:01:26Z","timestamp":1791820886000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000553578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":30,"URL":"https:\/\/doi.org\/10.1159\/000553578","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.33305760","asserted-by":"subject"}]},"ISSN":["0250-8095","1421-9670"],"issn-type":[{"value":"0250-8095","type":"print"},{"value":"1421-9670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}