Ji Xiaobing, Nie Shuai, Li Xiangxiang, Liu Hao, Du Xin, Fan Li
Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Critical Care Unit, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Nephrology (Carlton). 2025 Jun;30(6):e70054. doi: 10.1111/nep.70054.
Mesenchymal stem cell-derived exosome (MSC-exo) has garnered increasing attention because of its therapeutic potential for acute kidney injury (AKI). The aim of this study is to investigate the regulatory mechanism of MSC-exo in ischaemic AKI.
We first isolated MSC-exo and identified its properties through transmission electron microscopy observation, nanoparticle tracking analysis, PKH26 staining and Western blot analysis of surface markers. We also determined the therapeutic effect of MSC-exo on AKI through establishing an ischemia-reperfusion (I/R) animal model. The cell model was also constructed by hypoxia-reperfusion (H/R) and used for functional assays. Student's t-test and one-way ANOVA were used to analyse the data.
MSC-exo could alleviate the I/R-induced renal injury. In a cell model, MSC-exo could enhance proliferation, reduce apoptosis and block autophagy. Subsequently, miR-127-3p was determined to be transmitted by MSC-exo into injured renal cells to alleviate renal cell injury. Mechanism investigation revealed that miR-127-3p could directly target KIF3B to inactivate the Gli1-hedgehog pathway and thus transcriptionally inactivate ATG5 and ATG7.
MiR-127-3p transmitted by MSC-exo alleviates renal cell injury in AKI by suppressing ATG5/ATG7-mediated autophagy. This study explored a new molecular pathway associated with the therapeutic effect of MSC-exo on AKI, which might highlight the MSC-based therapeutic strategy for AKI.
间充质干细胞来源的外泌体（MSC-exo）因其对急性肾损伤（AKI）的治疗潜力而受到越来越多的关注。本研究旨在探讨MSC-exo在缺血性AKI中的调控机制。
我们首先分离出MSC-exo，并通过透射电子显微镜观察、纳米颗粒跟踪分析、PKH26染色和表面标志物的蛋白质印迹分析来鉴定其特性。我们还通过建立缺血再灌注（I/R）动物模型来确定MSC-exo对AKI的治疗效果。细胞模型也通过缺氧再灌注（H/R）构建并用于功能测定。采用学生t检验和单因素方差分析来分析数据。
MSC-exo可减轻I/R诱导的肾损伤。在细胞模型中，MSC-exo可促进增殖、减少凋亡并阻断自噬。随后，确定miR-127-3p由MSC-exo传递至受损肾细胞以减轻肾细胞损伤。机制研究表明，miR-127-3p可直接靶向KIF3B使Gli1-刺猬信号通路失活，从而转录失活ATG5和ATG7。
MSC-exo传递的miR-127-3p通过抑制ATG5/ATG7介导的自噬减轻AKI中的肾细胞损伤。本研究探索了一条与MSC-exo对AKI治疗作用相关的新分子途径，这可能突出了基于MSC的AKI治疗策略。
