miR-21 enhances cardiac fibrotic remodeling and fibroblast proliferation via CADM1/STAT3 pathway.
miR-21 enhances cardiac fibrotic remodeling and fibroblast proliferation via CADM1/STAT3 pathway.
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miR-21通过CADM1/STAT3途径增强心脏纤维化重塑和成纤维细胞增殖
DOI：
10.1186/s12872-017-0520-7
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发表时间：
2017-03-23
影响因子：
2.1
通讯作者：
Ge JJ
中科院分区：
文献类型：
--
作者：
Cao W;Shi P;Ge JJ
心脏纤维化在房颤的发病机制中起着关键作用，但其潜在的分子机制仍不清楚。然而，miR-21上调的潜在机制及其在心肌纤维化中的作用仍不清楚。方法采用免疫组织化学、实时荧光定量RT-PCR、细胞转染、细胞周期、细胞增殖和Western印迹等方法。结果证实肿瘤抑制细胞黏附分子1(CADM1)是miR-21的潜在靶点。我们的研究表明，miR-21调节CADM1的表达，而CADM1在心脏成纤维细胞和纤维化组织中的表达减少。转染miR-21的心脏成纤维细胞模拟促进miR-21过表达，增强STAT3的表达，降低CADM1的表达。然而，转染miR-21抑制剂的心脏成纤维细胞却获得了相反的表达结果。结论miR-21过表达通过下调CADM1的表达，通过STAT3信号通路促进心脏纤维化，提示miR-21是心脏纤维化重塑和房颤的重要信号分子。
BackgroundCardiac fibrosis play a key role in the atrial fibrillation pathogenesis but the underlying potential molecular mechanism is still understood. However, potential mechanisms for miR-21 upregulation and its role in cardiac fibrosis remain unclear. The controls cell proliferation and processes fundamental to disease progression.MethodsIn this study, immunohistochemistry, real-time RT-PCR, cell transfection, cell cycle, cell proliferation and Western blot were used, respectively.ResultsHere we have been demonstrated that the tumor suppressor cell adhesion molecule 1 (CADM1) is the potential target of miR-21. Our study revealed that miR-21 regulation of CADM1 expression, which was decreased in cardiac fibroblasts and fibrosis tissue. The cardiac fibroblasts transfected with miR-21 mimic promoted miR-21 overexpression enhanced STAT3 expression and decreased CADM1 expression. Nevertheless, the cardiac fibroblasts transfected with miR-21 inhibitor obtained the opposite expression result. Furthermore, downexpression of miR-21 suppressed cardiac fibroblast proliferation.ConclusionsThese results suggested that miR-21 overexpression promotes cardiac fibrosis via STAT3 signaling pathway by decrease CADM1 expression, indicating miR-21 as an important signaling molecule for cardiac fibrotic remodeling and AF.