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

INTRODUCTION: Hepatitis 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. METHODS: The mechanism of exosomes derived from bone marrow mesenchymal stem cell...

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Autores principales: Yang, Xiaoqian, Yu, Yani, Li, Baoshuang, Chen, Yueqi, Feng, Moxuan, Hu, Yongzheng, Jiang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183163/
https://www.ncbi.nlm.nih.gov/pubmed/37193022
http://dx.doi.org/10.7717/peerj.15314
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author Yang, Xiaoqian
Yu, Yani
Li, Baoshuang
Chen, Yueqi
Feng, Moxuan
Hu, Yongzheng
Jiang, Wei
author_facet Yang, Xiaoqian
Yu, Yani
Li, Baoshuang
Chen, Yueqi
Feng, Moxuan
Hu, Yongzheng
Jiang, Wei
author_sort Yang, Xiaoqian
collection PubMed
description INTRODUCTION: Hepatitis 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: BMSC-derived exosomes inhibit HBx-induced podocyte ferroptosis by transferring miR-223-3p.
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spelling pubmed-101831632023-05-15 Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis Yang, Xiaoqian Yu, Yani Li, Baoshuang Chen, Yueqi Feng, Moxuan Hu, Yongzheng Jiang, Wei PeerJ Biochemistry INTRODUCTION: Hepatitis 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: BMSC-derived exosomes inhibit HBx-induced podocyte ferroptosis by transferring miR-223-3p. PeerJ Inc. 2023-05-11 /pmc/articles/PMC10183163/ /pubmed/37193022 http://dx.doi.org/10.7717/peerj.15314 Text en ©2023 Yang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Yang, Xiaoqian
Yu, Yani
Li, Baoshuang
Chen, Yueqi
Feng, Moxuan
Hu, Yongzheng
Jiang, Wei
Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis
title Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis
title_full Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis
title_fullStr Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis
title_full_unstemmed Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis
title_short Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis
title_sort bone marrow mesenchymal stem cell-derived exosomes protect podocytes from hbx-induced ferroptosis
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183163/
https://www.ncbi.nlm.nih.gov/pubmed/37193022
http://dx.doi.org/10.7717/peerj.15314
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