Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis

BACKGROUND: The aim of this study was to explore the mechanism of complement C3a mediating podocyte injury during ischemia–reperfusion acute kidney injury (IR-AKI) and post-injury fibrosis. METHODS: Renal artery clamping was used to establish IR-AKI and post-injury fibrosis model. HE and Masson stai...

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Autores principales: Chen, Yi, Lin, Liyu, Rao, Siyi, Tao, Xuan, Cui, Jiong, Wan, Jianxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041728/
https://www.ncbi.nlm.nih.gov/pubmed/36973754
http://dx.doi.org/10.1186/s40001-023-01054-1
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author Chen, Yi
Lin, Liyu
Rao, Siyi
Tao, Xuan
Cui, Jiong
Wan, Jianxin
author_facet Chen, Yi
Lin, Liyu
Rao, Siyi
Tao, Xuan
Cui, Jiong
Wan, Jianxin
author_sort Chen, Yi
collection PubMed
description BACKGROUND: The aim of this study was to explore the mechanism of complement C3a mediating podocyte injury during ischemia–reperfusion acute kidney injury (IR-AKI) and post-injury fibrosis. METHODS: Renal artery clamping was used to establish IR-AKI and post-injury fibrosis model. HE and Masson staining were performed to observe renal fibrosis. The protein abundance levels were measured along with inflammatory markers, renal complement C3. Podocytes were treated with C3a with or without Toll-like receptor 4(TLR4) inhibitor. The effects of TLR4 up-regulation by TLR4 plasmids were examined. RESULTS: C3(−/−) resulted in amelioration of renal dysfunction by reducing podocyte damage and renal fibrosis. Immunoblot with renal tissue homogenates from IR-AKI mice revealed that C3(−/−) decreased TLR4/Nuclear Factor-κB (NFκB)-P65. CONCLUSION: Our results indicate that modulating C3/TLR4/NFκB-P65 signaling pathway is a novel therapeutic target for the IR-AKI and post-injury fibrosis. GRAPHICAL ABSTRACT: [Image: see text]
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spelling pubmed-100417282023-03-28 Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis Chen, Yi Lin, Liyu Rao, Siyi Tao, Xuan Cui, Jiong Wan, Jianxin Eur J Med Res Research BACKGROUND: The aim of this study was to explore the mechanism of complement C3a mediating podocyte injury during ischemia–reperfusion acute kidney injury (IR-AKI) and post-injury fibrosis. METHODS: Renal artery clamping was used to establish IR-AKI and post-injury fibrosis model. HE and Masson staining were performed to observe renal fibrosis. The protein abundance levels were measured along with inflammatory markers, renal complement C3. Podocytes were treated with C3a with or without Toll-like receptor 4(TLR4) inhibitor. The effects of TLR4 up-regulation by TLR4 plasmids were examined. RESULTS: C3(−/−) resulted in amelioration of renal dysfunction by reducing podocyte damage and renal fibrosis. Immunoblot with renal tissue homogenates from IR-AKI mice revealed that C3(−/−) decreased TLR4/Nuclear Factor-κB (NFκB)-P65. CONCLUSION: Our results indicate that modulating C3/TLR4/NFκB-P65 signaling pathway is a novel therapeutic target for the IR-AKI and post-injury fibrosis. GRAPHICAL ABSTRACT: [Image: see text] BioMed Central 2023-03-27 /pmc/articles/PMC10041728/ /pubmed/36973754 http://dx.doi.org/10.1186/s40001-023-01054-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chen, Yi
Lin, Liyu
Rao, Siyi
Tao, Xuan
Cui, Jiong
Wan, Jianxin
Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis
title Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis
title_full Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis
title_fullStr Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis
title_full_unstemmed Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis
title_short Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis
title_sort complement c3 mediates podocyte injury through tlr4/nfκb-p65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041728/
https://www.ncbi.nlm.nih.gov/pubmed/36973754
http://dx.doi.org/10.1186/s40001-023-01054-1
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