Department of Cardiology, Jinshan Hospital Affiliated to Fudan University, Shanghai, 201508, China.
Department of Cardiology, Jinshan Hospital Affiliated to Fudan University, Shanghai, 201508, China.
Biochem Biophys Res Commun. 2019 Oct 1;517(4):575-580. doi: 10.1016/j.bbrc.2019.07.053. Epub 2019 Aug 8.
Dilated cardiomyopathy (DCM) is considered as the final common response of myocardium to diverse genetic and environmental insults and characterized mainly by left ventricular systolic dysfunction. The current therapies for the treatment of DCM are costly high and outcomes are often unsatisfactory. To date, mesenchymal stem cells (MSCs) have been thought to be an ideal stem cell to repair damaged myocardium but was still within relatively small scales and few cases have been conducted in clinical trials. The use of erythropoietin (EPO), a growth factor produced in the kidneys have been found prevent cardiomyocyte apoptosis. This study was aimed to transplant MSCs into DCM rat bone marrow to express EPO in vivo and investigate the regulation of EPO on cell signaling pathways after transfection. The results found that transplantation of MSCs carrying EPO could significantly relief the cardiac dysfunctions of the DCM rat. This underylying mechanism involved with inhibiting p-NF-κB and p-P38, regulateing and promoting the anti-inflammatory balance, thereby alleviating tissue injury in DCM rats and exhibiting a protective role. Meanwhile, the MSCs + EPO treatment in DCM rat also activated the p-Akt pathway and thus protecting the myocardium from apoptosis in DCM rats. The study revealed an potential therapeutic effect of MSCs and EPO in clinical and provided a molecular mechanism of action for treating DCM.
扩张型心肌病（DCM）被认为是心肌对多种遗传和环境损伤的最终共同反应，主要表现为左心室收缩功能障碍。目前治疗 DCM 的方法费用高，疗效往往不尽人意。迄今为止，间充质干细胞（MSCs）被认为是修复受损心肌的理想干细胞，但仍处于相对较小的规模，临床试验的案例也很少。促红细胞生成素（EPO）是一种在肾脏中产生的生长因子，已被发现可防止心肌细胞凋亡。本研究旨在将 MSCs 移植到 DCM 大鼠骨髓中，在体内表达 EPO，并研究转染后 EPO 对细胞信号通路的调节作用。结果发现，移植携带 EPO 的 MSCs 可显著缓解 DCM 大鼠的心脏功能障碍。这种潜在的机制涉及抑制 p-NF-κB 和 p-P38，调节和促进抗炎平衡，从而减轻 DCM 大鼠的组织损伤并发挥保护作用。同时，DCM 大鼠的 MSCs+EPO 治疗也激活了 p-Akt 通路，从而防止 DCM 大鼠的心肌细胞凋亡。该研究揭示了 MSCs 和 EPO 在临床治疗中的潜在疗效，并为治疗 DCM 提供了作用的分子机制。
