Liu Xin, Bian Hong, Zhou Tingyuan, Zhao Chunjuan
Biochemistry and Molecular Biology Basic Medical Institute of Ningxia Medical University Yinchun Ningxia China.
Cardiothoracic Surgery Southern University of Science and Technology Hospital Shenzhen and Guangzhou Guangdong China.
FASEB Bioadv. 2025 Apr 15;7(5):e70010. doi: 10.1096/fba.2024-00235. eCollection 2025 May.
Overexpression of spike glycoprotein G of vesicular stomatitis virus (VSVG) can induce the release of fusogenic plasma membrane vesicles (fPMVs), which can transport cytoplasmic, nuclear, and surface proteins directly to target cells. This study aimed to investigate the roles of rat bone marrow mesenchymal stem cells (rBMSCs)-derived fPMVs containing VSVG protein in myocardial injury and their related mechanisms. The plasmids of pLP-VSVG were used to transfect rBMSCs, and then fPMVs were obtained by mechanical extrusion. After that, H9c2 cells were first treated with hypoxia reoxygenation (HR) to establish a cardiomyocyte injury model, and then were treated with fPMVs to evaluate the rescue of rBMSCs-derived fPMVs on HR-induced cardiomyocyte injury. FPMVs containing VSVG protein were successfully prepared from rBMSCs with VSVG overexpression. Compared with control fPMVs, , , VSVG, CD81, MTCO1, and TOMM20 were significantly up-regulated ( < 0.05), while eEF2 was significantly down-regulated ( < 0.05) in the fPMVs containing VSVG protein. Additionally, it was obvious fPMVs could carry mitochondria into H9c2 cells, and HR treatment significantly inhibited viability and induced apoptosis of H9c2 cells, as well as significantly increased the contents of TNF-α and IL-1β, and ROS levels both in cells and cellular mitochondria, while evidently reducing the levels of ATP, MRCC IV, and ( < 0.05). However, fPVMs could remarkably reverse the changes in these indexes caused by HR ( < 0.05). RBMSCs-derived fPMVs containing VSVG protein may have protective effects on myocardial injury by mediating mitochondrial transfer and regulating mitochondrial functions.
水泡性口炎病毒(VSVG)的刺突糖蛋白G的过表达可诱导融合性质膜囊泡(fPMVs)的释放,其可将细胞质、细胞核和表面蛋白直接转运至靶细胞。本研究旨在探讨含VSVG蛋白的大鼠骨髓间充质干细胞(rBMSCs)来源的fPMVs在心肌损伤中的作用及其相关机制。用pLP-VSVG质粒转染rBMSCs,然后通过机械挤压获得fPMVs。之后,首先用缺氧复氧(HR)处理H9c2细胞以建立心肌细胞损伤模型,然后用fPMVs处理以评估rBMSCs来源的fPMVs对HR诱导的心肌细胞损伤的挽救作用。成功从过表达VSVG的rBMSCs制备了含VSVG蛋白的fPMVs。与对照fPMVs相比,含VSVG蛋白的fPMVs中VSVG、CD81、MTCO1和TOMM20显著上调(P<0.05),而eEF2显著下调(P<0.05)。此外,明显可见fPMVs可将线粒体携带至H9c2细胞中,HR处理显著抑制H9c2细胞的活力并诱导其凋亡,同时显著增加细胞和细胞线粒体中TNF-α和IL-1β的含量以及ROS水平,而明显降低ATP、MRCC IV和(P<0.05)的水平。然而,fPVMs可显著逆转HR引起的这些指标的变化(P<0.05)。含VSVG蛋白的rBMSCs来源的fPMVs可能通过介导线粒体转移和调节线粒体功能对心肌损伤具有保护作用。