{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T19:33:52Z","timestamp":1776713632516,"version":"3.51.2"},"reference-count":74,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,9,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Clinically, myocardial fibrosis is one of the most common complications caused by chronic kidney disease (CKD). However, the potential mechanisms of CKD\u2010induced myocardial fibrosis have not been clarified.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">In our in vivo study, a rat model of CKD with 5\/6 nephrectomy was established. The CKD model was treated with the glioma 1 (Gli\u20101) inhibitor GANT\u201061, and myocardial fibrosis and serum intact fibroblast growth factor 23 levels were assessed 16\u2009weeks after nephrectomy. Finally, we found that Gli\u20101 and Smoothened in the Sonic Hedgehog (Shh) signaling pathway were activated and that collagen\u20101 and collagen\u20103, which constitute the fibrotic index, were expressed in CKD myocardial tissue. After administering the Gli\u20101 inhibitor GANT\u201061, the degree of myocardial fibrosis was reduced, and Gli\u20101 expression was also inhibited. We also measured blood pressure, cardiac biomarkers, and other indicators in rats and performed hematoxylin\u2010eosin staining of myocardial tissue. Furthermore, in vitro studies showed that intact fibroblast growth factor 23 promoted cardiac fibroblast proliferation and transdifferentiation into myofibroblasts by activating the Shh signaling pathway, thereby promoting cardiac fibrosis, as manifested by increased expression of the Shh, Patch 1, and Gli\u20101 mRNAs and Shh, Smoothened, and Gli\u20101 proteins in the Shh signaling pathway. The protein and mRNA levels of other fibrosis indicators, such as \u03b1\u2010smooth muscle actin, which are also markers of transdifferentiation, collagen\u20101, and collagen\u20103, were increased.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">On the basis of these results, intact fibroblast growth factor 23 promotes CKD\u2010induced myocardial fibrosis by activating the Shh signaling pathway.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.026365","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T09:43:32Z","timestamp":1663148612000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Intact Fibroblast Growth Factor 23 Regulates Chronic Kidney Disease\u2013Induced Myocardial Fibrosis by Activating the Sonic Hedgehog Signaling Pathway"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5978-225X","authenticated-orcid":false,"given":"Lanlan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-6193","authenticated-orcid":false,"given":"Hua","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158765"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02663-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012020145"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2369-14-280"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2016.07.012"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13069-015-0029-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2018.08.007"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-005-2351-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.06.003"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00708-3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.12.039"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1313"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2984"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1693608"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2015.14"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26506"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/384129a0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/35077219"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-014-1433-1"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.7.1313"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.03.007"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154048"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.20.4808"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071816-064620"},{"key":"e_1_3_2_26_2","first-page":"227","article-title":"The relationship between FGF\u201023 and ghrelin levels in CKD patients: preliminary data","volume":"68","author":"Ozturk S","year":"2016","unstructured":"Ozturk S, Ozkan O, Efe M, Yazici H, Gursu M, Kaya AH, Cebeci E, Sumnu A, Karadag S, Poturoglu S, et al. 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