Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis

PeerJ

article

Xiaoqian Yang¹  Yani Yu¹  Baoshuang Li¹  Yueqi Chen¹  Moxuan Feng¹  Yongzheng Hu¹  Wei Jiang¹ 

[1] Department of Nephrology, The Affiliated Hospital of Qingdao University

关键词: Exosomes;    Ferroptosis;    HBx;    Bone marrow mesenchymal stem cells;    miR-223-3p;   

DOI  :  10.7717/peerj.15314

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

IntroductionHepatitis B virus-associated glomerulonephritis (HBV-GN) is a common secondary kidney disease in China, the pathogenesis of which is not completely clear, and there is still a lack of effective treatment.MethodsThe mechanism of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) was investigated by using HBx-transfected human renal podocytes. Cell viability was detected by CCK8 assay. Iron and malondialdehyde (MDA) contents were detected by using commercial kits. Reactive oxygen species (ROS) levels were measured by flow cytometry analysis. The expression of ferroptosis related molecules was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The effect of miR-223-3p transferred by BMSC-derived exosomes on HBx-overexpressing podocytes was proved by using miR-223-3p inhibitor.ResultsThe cell viability of podocytes reduced at 72 h or 96 h after the transfection of lentivirus overexpressing HBx protein (p < 0.05). Ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were down-regulated upon HBx overexpression, while acyl-CoA synthetase long-chain family member 4 (ACSL4) was up-regulated (p < 0.05). Intracellular levels of iron, MDA, and ROS were also enhanced (p < 0.05). BMSC-derived exosomes protected against ferroptosis induced by HBx overexpression in podocytes. miR-223-3p was enriched in BMSC-derived exosomes. Application of miR-223-3p inhibitor reversed the protective effect of BMSC-derived exosomes on HBx-induced ferroptosis in podocytes.ConclusionBMSC-derived exosomes inhibit HBx-induced podocyte ferroptosis by transferring miR-223-3p.

【 授权许可】

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