Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia–reperfusion acute kidney injury and post-injury fibrosis
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Published:2023-03-27
Issue:1
Volume:28
Page:
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ISSN:2047-783X
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Container-title:European Journal of Medical Research
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language:en
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Short-container-title:Eur J Med Res
Author:
Chen Yi,Lin Liyu,Rao Siyi,Tao Xuan,Cui Jiong,Wan Jianxin
Abstract
Abstract
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
Publisher
Springer Science and Business Media LLC
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