Department of Intensive Care Unit of Cardiac Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, No. 96, Dongchuan Road, Guangzhou, 510080, People's Republic of China.
Department of Cardiac Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, 510080, People's Republic of China.
J Cardiovasc Transl Res. 2022 Apr;15(2):302-316. doi: 10.1007/s12265-021-10156-2. Epub 2021 Sep 10.
The purpose of the present study was to define the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in the progression of myocardial infarction (MI)-induced cardiac fibrosis. An in vitro cell model of hypoxia-induced cardiac fibrosis was constructed in cardiac fibroblasts (CFs). miR-212-5p was poorly expressed in clinical pathological samples and animal models of cardiac fibrosis caused by MI, while miR-212-5p expression was enriched in EVs released from MSCs. EVs from MSCs were isolated, evaluated, and co-cultured with CFs. Dual-luciferase reporter gene assay revealed that miR-212-5p negatively targeted NLRC5 progression of cardiac fibrosis. Following loss- and gain-function assay, EVs expressing miR-212-5p protected against cardiac fibrosis evidenced by reduced levels of α-SMA, Collagen I, TGF-β1, and IL-1β. In vivo experiments further confirmed the above research results. Collectively, EVs from MSCs expressing miR-212-5p may attenuate MI by suppressing the NLRC5/VEGF/TGF-β1/SMAD axis.
本研究旨在确定间充质干细胞（MSC）衍生的细胞外囊泡（EVs）在心肌梗死（MI）诱导的心肌纤维化进展中的作用。构建了心肌成纤维细胞（CFs）缺氧诱导的心肌纤维化体外细胞模型。miR-212-5p 在 MI 引起的心脏纤维化的临床病理样本和动物模型中表达水平较低，而 MSC 释放的 EVs 中 miR-212-5p 表达丰富。分离、评估 MSC 的 EVs，并与 CFs 共培养。双荧光素酶报告基因检测显示 miR-212-5p 负调控 NLRC5 促进心脏纤维化。通过降低 α-SMA、Collagen I、TGF-β1 和 IL-1β 的水平，表达 miR-212-5p 的 EVs 可减轻心脏纤维化。体内实验进一步证实了上述研究结果。综上所述，表达 miR-212-5p 的 MSC 的 EVs 可能通过抑制 NLRC5/VEGF/TGF-β1/SMAD 轴来减轻 MI。
