title: FGF23 promotes myocardial fibrosis in mice through activation of β-catenin.
abstract: Fibroblast growth factor 23 (FGF23) has been reported to induce left ventricular hypertrophy, but it remains unclear whether FGF23 plays a role in cardiac fibrosis. This study is attempted to investigate the role of FGF23 in post-infarct myocardial fibrosis in mice. We noted that myocardial and plasma FGF23 and FGF receptor 4 were increased in mice with heart failure as well as in cultured adult mouse cardiac fibroblasts (AMCFs) exposed to angiotensin II, phenylephrine, soluble fractalkine. Recombinant FGF23 protein increased active β-catenin , procollagen I and procollagen III expression in cultured AMCFs. Furthermore, intra-myocardial injection of adeno-associated virus-FGF23 in mice significantly increased left ventricular end-diastolic pressure and myocardial fibrosis, and markedly upregulated active β-catenin, transforming growth factor β (TGF-β), procollagen I and procollagen III in both myocardial infarction (MI) and ischemia/reperfusion (IR) mice, while β-catenin inhibitor or silencing of β-catenin antagonized the FGF23-promoted myocardial fibrosis in vitro and in vivo. These findings indicate that FGF23 promotes myocardial fibrosis and exacerbates diastolic dysfunction induced by MI or IR, which is associated with the upregulation of active β-catenin and TGF-β.
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Huixin
authors: H
authors: Hao
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Xixian
authors: X
authors: Li
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Qingman
authors: Q
authors: Li
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Hairuo
authors: H
authors: Lin
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Zhenhuan
authors: Z
authors: Chen
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Jiahe
authors: J
authors: Xie
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Wanling
authors: W
authors: Xuan
authors: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Wangjun
authors: W
authors: Liao
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Jianping
authors: J
authors: Bin
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Xiaobo
authors: X
authors: Huang
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Cardiovascular Division of the Department of Medicine, National Cerebral and Cardiovascular Center, Fujishirodai, Suita, Osaka, Japan.
authors: Masafumi
authors: M
authors: Kitakaze
authors: State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Yulin
authors: Y
authors: Liao
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology*; D005355:Fibrosis; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology*; D010656:Phenylephrine / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000097:blood; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D000804:Angiotensin II; D010656:Phenylephrine; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D003094:Collagen; C496372:Fgfr4 protein, mouse; D051499:Receptor, Fibroblast Growth Factor, Type 4
keywords: Pathology Section; TGF-β; fibroblast growth factor 23; ischemia/reperfusion; myocardial fibrosis; β-catenin