FGF23 promotes myocardial fibrosis in mice through activation of β-catenin

Huixin Hao, Xixian Li, Qingman Li, Hairuo Lin, Zhenhuan Chen, Jiahe Xie, Wanling Xuan, Wangjun Liao, Jianping Bin, Xiaobo Huang, Masafumi Kitakaze, Yulin Liao

Research output: Contribution to journalArticle

34 Scopus citations

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 adenoassociated 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.

Original languageEnglish (US)
Pages (from-to)64649-64664
Number of pages16
JournalOncotarget
Volume7
Issue number40
DOIs
StatePublished - 2016

Keywords

  • Fibroblast growth factor 23
  • Ischemia/reperfusion
  • Myocardial fibrosis
  • Pathology Section
  • TGF-β
  • β-catenin

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Hao, H., Li, X., Li, Q., Lin, H., Chen, Z., Xie, J., Xuan, W., Liao, W., Bin, J., Huang, X., Kitakaze, M., & Liao, Y. (2016). FGF23 promotes myocardial fibrosis in mice through activation of β-catenin. Oncotarget, 7(40), 64649-64664. https://doi.org/10.18632/oncotarget.11623