Abstract

Ischaemia-reperfusion injury (IRI) is closely related to cardiovascular disease (CVD), which is the leading cause of death and disability. Exosomes appear to be involved in several diseases, including CVD. However, the role of mesenchymal stem cell (MSC)-derived exosomes in IRI remains unclear. miRNA expression levels in exosomes from rat normal MSCs or hypoxia-reoxygenation (H/R) MSCs were determined by qPCR and the two significantly upregulated miRNAs were selected for further investigation. Rat cardiomyoblasts (H9c2) were transfected with either miRNA mimics or scramble controls, followed by H/R induction. The effects of miRNA overexpression and exosome administration on H/R damage were then investigated. H/R increased Faslg, suppressed β-catenin, inhibited cell proliferation and migration, and stimulated apoptosis and reactive oxygen species (ROS) production. miR-149 or Let-7c mimics or exosomes reversed H/R-induced damage. The luciferase reporter assay proved the targeted regulation of Faslg by both miR149 and Let-7c. Inhibition of β-catenin suppressed cell migration, proliferation, and ΔΨm but increased apoptosis and ROS. Overall, bone marrow MSC-derived exosomes protected rat cardiomyoblasts from H/R injury via the miR-149/Let-7c/Faslg axis.

摘要

缺血再灌注损伤（IRI）与心血管疾病（CVD）密切相关，心血管疾病是导致死亡和残疾的主要原因。外泌体似乎与多种疾病有关，包括心血管疾病。然而，间充质干细胞（MSC）衍生的外泌体在 IRI 中的作用仍不清楚。通过 qPCR 确定来自大鼠正常 MSC 或缺氧复氧 (H/R) MSC 的外泌体中的 miRNA 表达水平，并选择两种显着上调的 miRNA 进行进一步研究。大鼠心肌细胞 (H9c2) 用 miRNA 模拟物或加扰对照转染，然后进行 H/R 诱导。然后研究了 miRNA 过表达和外泌体给药对 H/R 损伤的影响。H/R 增加 Faslg，抑制 β-catenin，抑制细胞增殖和迁移，并刺激细胞凋亡和活性氧 (ROS) 的产生。miR-149 或 Let-7c 模拟物或外泌体逆转了 H/R 诱导的损伤。荧光素酶报告基因检测证明了 miR149 和 Let-7c 对 Faslg 的靶向调节。β-catenin 的抑制抑制了细胞迁移、增殖和 ΔΨm，但增加了细胞凋亡和 ROS。总体而言，骨髓 MSC 衍生的外泌体保护大鼠心肌细胞免受 H/R 损伤通过miR-149/Let-7c/Faslg 轴。