{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:51:40Z","timestamp":1791312700282,"version":"4.3.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":57,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2019C03012"],"award-info":[{"award-number":["2019C03012"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003750"],"award-info":[{"award-number":["82003750"]}],"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":["81671403"],"award-info":[{"award-number":["81671403"]}],"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":["82070446"],"award-info":[{"award-number":["82070446"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007194","name":"Wenzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["Y20210136"],"award-info":[{"award-number":["Y20210136"]}],"id":[{"id":"10.13039\/501100007194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ21H020009"],"award-info":[{"award-number":["LQ21H020009"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY22H020004"],"award-info":[{"award-number":["LY22H020004"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    With the progression of chronic kidney disease (CKD), we can often observe cardiac remodeling, fibrosis, and cardiac failure in patients. Cysteine\u2010rich protein 61 (CCN1) is an extracellular matrix protein that plays a reuse role in cardiac remodeling. However, whether CCN1 participates in the crosslink between the heart and kidney in CKD and the potential mechanism remains unknown.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We constructed a mouse model of CKD by 5\/6 nephrectomy (5\/6 Nx). Hematoxylin\u2013eosin staining (H&amp;E), Masson\u2019s trichrome staining, and Sirius red staining were used to observe cardiac morphology and fibrosis. H9c2 cells were treated with si\u2010CCN1 or si\u2010NC or mitogen\u2010activated protein kinase (MAPK)\u2013related inhibitors or agonist before being cultured with 5\/6 Nx mouse serum. The relative protein level was detected by Western blotting.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    We observed that CCN1 expression was markedly enhanced in the serum and heart tissues, accompanied by disordered myocardial arrangement, obvious cardiac fibrosis, hypertrophy, and decreased cardiac systolic function reflected by echocardiography. The relative markers collagen 1 (COL\u20101), transforming growth factor\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ), heavy\u2010chain cardiac myosin (MyHC), and atrial natriuretic peptide (ANP) presented an increase in expression. In vivo and in vitro, after the knockdown of CCN1, the above results in the CKD group or CKD serum group were reversed; in addition, the MAPK signaling pathway was obviously activated due to 5\/6 Nx, which was abolished by CCN1 inhibition. CCN1 silencing or MAPK pathway inhibition also decreased the expression of myocardial fibrosis and hypertrophy markers in H9c2 cells, while MAPK\u2010related agonist partly reversed the effect of CCN1 inhibition.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Our in vivo and in vitro study showed that specific CCN1 deficiency markedly alleviated cardiac remodeling in 5\/6 Nx mice through the inhibition of the MAPK pathway.\n                  <\/jats:p>","DOI":"10.1155\/cdr\/6813183","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T06:39:04Z","timestamp":1740983944000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cysteine\u2010Rich Protein 61 (CCN1) Deficiency Alleviated Cardiac Remodeling in 5\/6 Nephrectomized Mice by Suppressing the MAPK Signaling Pathway"],"prefix":"10.1155","volume":"2025","author":[{"given":"Yihan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincheng","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2448-2071","authenticated-orcid":false,"given":"Zhen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-1377","authenticated-orcid":false,"given":"Zhouqing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30788-2"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.273078"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2011.05487.x"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019020117"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)00033-4"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(18)30391-8"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12070439"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.4.8731"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-09-0017"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0778-3"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000248426.35019.89"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.24.8709-8720.2002"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000127952.90508.9D"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1159\/000491984"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.5603\/FHC.2012.0014"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt001"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000501929"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.3791\/55825-v"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00066.2013"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.14180920"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306565"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140045"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1139\/Y09-105"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.2310\/JIM.0b013e318250b101"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20709"},{"key":"e_1_2_14_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-018-0450-x"},{"key":"e_1_2_14_27_2","doi-asserted-by":"publisher","DOI":"10.3109\/10799893.2015.1030412"},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00054.2009"},{"key":"e_1_2_14_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3495"},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.231514"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00149"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.211086598"},{"key":"e_1_2_14_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg474"},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8697257"},{"key":"e_1_2_14_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.02.029"}],"container-title":["Cardiovascular 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