Abstract Cardiac fibrosis is a pathological feature common to a variety of heart diseases such as myocardial infarction, arrhythmias, cardiomyopathies and heart failure. The molecular mechanism underlying the cardiac fibrosis is still unclear. Forkhead box F1 (FOXF1), a member of the forkhead transcription factor superfamily, plays critical roles in the development of hepatic fibrosis. However, whether FOXF1 is involved in the pathogenesis of cardiac fibrosis remains to be elucidated. The present study aimed to investigate the role of FOXF1 and its mechanisms in regulating cardiac fibrosis. The results demonstrated that FOXF1 was downregulated in Ang II-induced CFs. Overexpression of FOXF1 inhibited angiotensin II (Ang II)-induced proliferation, migration and oxidative stress in cardiac fibroblasts (CFs). Overexpression of FOXF1 also reduced the expression of alpha-smooth muscle actin (a-SMA) in Ang II-induced CFs, suggesting that overexpression of FOXF1 prevented the differentiation of CFs to myofibroblasts. Furthermore, the production of extracellular matrix (ECM) components including type I collagen and fibronectin were reduced by overexpression of FOXF1 in Ang II-induced CFs. Furthermore, overexpression of FOXF1 prevented Ang II-induced activation of transforming growth factor beta 1 (TGF-β1)/Smad3 pathway in CFs. In conclusion, the results of the present study indicated that FOXF1 acted as a key regulator of pathological cardiac fibrosis, and overexpression of FOXF1 ameliorated cardiac fibrosis by inhabiting the TGF-β1/Smad3 signaling pathway. These results indicated that FOXF1 may be a novel target for attenuating cardiac fibrosis.

中文翻译：

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FOXF1通过抑制TGF-β1/Smad3信号通路改善血管紧张素II诱导的心脏成纤维细胞心脏纤维化

摘要 心脏纤维化是心肌梗塞、心律失常、心肌病和心力衰竭等多种心脏疾病的共同病理特征。心脏纤维化的分子机制尚不清楚。Forkhead box F1 (FOXF1) 是叉头转录因子超家族的成员，在肝纤维化的发展中起着关键作用。然而，FOXF1 是否参与心脏纤维化的发病机制仍有待阐明。本研究旨在探讨 FOXF1 的作用及其在调节心脏纤维化中的机制。结果表明 FOXF1 在 Ang II 诱导的 CF 中下调。FOXF1 的过表达抑制了血管紧张素 II (Ang II) 诱导的心脏成纤维细胞 (CFs) 的增殖、迁移和氧化应激。FOXF1 的过表达还降低了 Ang II 诱导的 CF 中 α-平滑肌肌动蛋白 (a-SMA) 的表达，表明 FOXF1 的过表达阻止了 CF 向肌成纤维细胞的分化。此外，通过在 Ang II 诱导的 CF 中过表达 FOXF1，减少了细胞外基质 (ECM) 成分的产生，包括 I 型胶原蛋白和纤连蛋白。此外，FOXF1 的过表达阻止了 Ang II 诱导的 CF 中转化生长因子β1（TGF-β1）/Smad3 通路的激活。总之，本研究结果表明 FOXF1 作为病理性心脏纤维化的关键调节因子，FOXF1 的过表达通过抑制 TGF-β1/Smad3 信号通路改善心脏纤维化。这些结果表明 FOXF1 可能是减轻心脏纤维化的新靶点。