circCELF1 通过调控 FTO/mA 和 miR-636 表达抑制心肌纤维化。
circCELF1 Inhibits Myocardial Fibrosis by Regulating the Expression of DKK2 Through FTO/mA and miR-636.
机构信息
Department of Cardiology, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong, China.
Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan, 750000, Ningxia, China.
出版信息
J Cardiovasc Transl Res. 2022 Oct;15(5):998-1009. doi: 10.1007/s12265-022-10209-0. Epub 2022 Feb 7.
The aim of this study is to explore the role of circCELF1/miR-636/DKK2 pathway in myocardial fibrosis (MF). RT-qPCR and western blot were used to detect the expression of circCELF1, miR-636, and DKK2 in activated cardiac fibroblasts (CFs) and the hearts of acute myocardial infarction (AMI) mice. The mA level of DKK2 was detected by RIP and RT-qPCR. The regulation of circCELF1/miR-636/DKK2 pathway on CF viability, activation, apoptosis, and migration was verified by CCK-8, western blot, flow cytometry, and Transwell. Ang II induced downregulation of circCELF1 expression, while circCELF1 enhanced the expression of DKK2 by adsorbing miR-636. circCELF1 also reduced DKK2 mA level by upregulating FTO expression, thereby inhibiting the binding of miR-636 to DKK2 and promoting DKK2 expression. Ang II promoted CF viability, activation, and migration through the circCELF1/miR-636/DKK2 pathway. Both miR-636 inhibitors and DKK2 effectively reduced MF and improved cardiac function in AMI mice.
本研究旨在探讨 circCELF1/miR-636/DKK2 通路在心肌纤维化 (MF) 中的作用。使用 RT-qPCR 和 Western blot 检测激活的心肌成纤维细胞 (CFs)和急性心肌梗死 (AMI) 小鼠心脏中 circCELF1、miR-636 和 DKK2 的表达。通过 RIP 和 RT-qPCR 检测 DKK2 的 mA 水平。通过 CCK-8、Western blot、流式细胞术和 Transwell 验证 circCELF1/miR-636/DKK2 通路对 CF 活力、激活、凋亡和迁移的调节作用。Ang II 下调 circCELF1 的表达，而 circCELF1 通过吸附 miR-636 增强 DKK2 的表达。circCELF1 还通过上调 FTO 表达降低 DKK2 的 mA 水平，从而抑制 miR-636 与 DKK2 的结合并促进 DKK2 表达。Ang II 通过 circCELF1/miR-636/DKK2 通路促进 CF 活力、激活和迁移。miR-636 抑制剂和 DKK2 均可有效减轻 AMI 小鼠的 MF 并改善心功能。
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