Complement C3 mediates podocyte injury through TLR4/NF?B-P65 signaling during ischemia-reper fusion 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 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-?B (NF?B)-P65.Conclusion Our results indicate that modulating C3/TLR4/NF?B-P65 signaling pathway is a novel therapeutic target for the IR-AKI and post-injury fibrosis.

Automated summary

This study aimed to investigate the mechanism of how complement C3a mediates podocyte injury during ischemia-reperfusion acute kidney injury (IR-AKI) and post-injury fibrosis. An IR-AKI and post-injury fibrosis model was established using renal artery clamping. The results showed that C3(-/-) led to improvement in renal dysfunction by reducing podocyte damage and renal fibrosis. Immunoblot analysis indicated that C3(-/-) decreased TLR4/NF?B-P65 in renal tissue homogenates from IR-AKI mice.