Department of Cadre Ward, the First Hospital of Jilin University, Changchun, China.
Chronic Diseases Clinic, Jilin Province Faw General Hospital, Changchun, China.
Phytother Res. 2024 Apr;38(4):1745-1760. doi: 10.1002/ptr.8018. Epub 2023 Sep 22.
Diabetic cardiomyopathy (DCM) is a cardiac complication resulting from long-term uncontrolled diabetes, characterized by myocardial fibrosis and abnormal cardiac function. This study aimed at investigating the potential of ginsenoside RG1 (RG1)-induced mesenchymal stem cells (MSCs) in alleviating DCM. A DCM mouse model was constructed, and the effects of RG1-induced MSCs on myocardial function and fibrosis in diabetic mice were evaluated. RG1-induced MSCs were cocultured with high glucose-treated fibroblasts for subsequent functional and mechanism assays. It was discovered that RG1-induced MSCs secrete exosomes that induce macrophage M2 polarization. Mechanistically, exosomes derived from RG1-induced MSCs transferred circNOTCH1 into macrophages, activating the NOTCH signaling pathway. A competing endogenous RNA (ceRNA) regulatory axis consisting of circNOTCH1, miR-495-3p, and NOTCH1 was found to contribute to DCM alleviation.. This study unveiled that exosomal circNOTCH1 secreted by RG1-induced MSCs can alleviate DCM by activating the NOTCH signaling pathway to induce macrophage M2 polarization. This finding may contribute to the development of new therapeutic approaches for DCM.
糖尿病心肌病（DCM）是一种由长期未控制的糖尿病引起的心脏并发症，其特征是心肌纤维化和心脏功能异常。本研究旨在探讨 RG1 诱导的间充质干细胞（MSC）在缓解 DCM 中的潜力。构建了 DCM 小鼠模型，评估了 RG1 诱导的 MSC 对糖尿病小鼠心肌功能和纤维化的影响。将 RG1 诱导的 MSC 与高糖处理的成纤维细胞共培养，进行后续的功能和机制分析。研究发现，RG1 诱导的 MSC 分泌的外泌体可诱导巨噬细胞 M2 极化。从机制上看，RG1 诱导的 MSC 来源的外泌体将 circNOTCH1 转移到巨噬细胞中，激活 NOTCH 信号通路。研究还发现一个包含 circNOTCH1、miR-495-3p 和 NOTCH1 的竞争性内源性 RNA（ceRNA）调控轴，该轴有助于缓解 DCM。本研究揭示了 RG1 诱导的 MSC 分泌的外泌体 circNOTCH1 通过激活 NOTCH 信号通路诱导巨噬细胞 M2 极化，从而缓解 DCM。这一发现可能为 DCM 的治疗方法提供新的思路。
