FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways
FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways
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FGF23 通过介导 STAT3 和 SMAD3 通路调节心房颤动中的心房纤维化
DOI：
10.1002/jcp.28548
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Cheng, Xiaoshu
中科院分区：
文献类型：
--
作者：
Dong, Quanbin;Li, Shaochuan;Cheng, Xiaoshu
高成纤维细胞生长因子23 （FGF23）浓度是房颤（AF）的一个强有力的预测因子，但研究人员尚未明确FGF23导致房颤患者心房纤维化的机制。本研究旨在阐明FGF23诱导房颤患者心房纤维化的机制。将心肌成纤维细胞（CFs）与不同浓度的重组FGF23蛋白共培养。与SR组相比，AF组FGF23、FGFR4、α‐平滑肌肌动蛋白（α‐SMA）和胶原‐1水平显著升高。暴露于高浓度的重组FGF23蛋白增加了活性氧（ROS）的积累，激活了α‐SMA、胶原‐1、信号转导和转录激活因子3 （STAT3）和SMAD3信号。高浓度重组FGF23蛋白刺激的cf中纤维化蛋白水平被N‐乙酰半胱氨酸（NAC，一种ROS抑制剂）、船舶信息系统3（一种SMAD3抑制剂）和Stattic（一种STAT3抑制剂）逆转。此外，与未处理的cf相比，重组FGF23蛋白处理的cf的特点是STAT3和SMAD3之间的相互作用增加。基于这些结果，FGF23通过增加ROS的产生并随后激活STAT3和SMAD3信号传导，诱导房颤患者心房纤维化。
High fibroblast growth factor 23 (FGF23) concentrations are a strong predictor of atrial fibrillation (AF), but researchers have not clearly determined the mechanism by which FGF23 causes atrial fibrosis in patients with AF. This study aims to elucidate the mechanism by which FGF23 induces atrial fibrosis in patients with AF. Immunohistochemistry was used to study the expression of FGF23, FGFR4, and fibrotic factors in patients with a normal sinus rhythm (SR) and patients with AF. Cardiac fibroblasts (CFs) were cocultured with different concentrations of the recombinant FGF23 protein. Compared with the SR group, the levels of FGF23, FGFR4, α‐smooth muscle actin (α‐SMA), and collagen‐1 were significantly increased in the AF group. Exposure to high concentrations of the recombinant FGF23 protein increased the accumulation of reactive oxygen species (ROS) and activated α‐SMA, collagen‐1, signal transducer and activator of transcription 3 (STAT3) and SMAD3 signaling in cultured CFs. The levels of fibrotic proteins in CFs stimulated with high concentrations of the recombinant FGF23 protein were reversed by N‐acetylcysteine (NAC, a ROS inhibitor), ship information system 3 (a SMAD3 inhibitor), and Stattic (a STAT3 inhibitor). Furthermore, compared to untreated CFs, CFs treated with the recombinant FGF23 protein were characterized by an increased interaction between STAT3 and SMAD3. Based on these results, FGF23 induces atrial fibrosis in patients with AF by increasing ROS production and subsequently activating STAT3 and SMAD3 signaling.