Cao Wei, Shi Peng, Ge Jian-Jun
Department of Cardiology, The first Hospital of Anhui Medical University, Hefei, 230031, China.
Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei, 230601, China.
BMC Cardiovasc Disord. 2017 Mar 23;17(1):88. doi: 10.1186/s12872-017-0520-7.
Cardiac 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.
In this study, immunohistochemistry, real-time RT-PCR, cell transfection, cell cycle, cell proliferation and Western blot were used, respectively.
Here 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.
These 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.
心脏纤维化在房颤发病机制中起关键作用，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脏纤维化中的作用仍不明确。其控制细胞增殖及疾病进展的基本过程。
在本研究中，分别使用了免疫组织化学、实时逆转录聚合酶链反应、细胞转染、细胞周期、细胞增殖和蛋白质印迹法。
我们在此证明肿瘤抑制细胞粘附分子1（CADM1）是miR-21的潜在靶点。我们的研究表明，miR-21对CADM1表达有调控作用，其在心脏成纤维细胞和纤维化组织中表达降低。用miR-21模拟物转染的心脏成纤维细胞促进了miR-21过表达，增强了信号转导和转录激活因子3（STAT3）表达并降低了CADM1表达。然而，用miR-21抑制剂转染的心脏成纤维细胞得到了相反的表达结果。此外，miR-21的下调抑制了心脏成纤维细胞增殖。
这些结果表明，miR-21过表达通过降低CADM1表达，经由STAT3信号通路促进心脏纤维化，表明miR-21是心脏纤维化重塑和房颤的重要信号分子。
