ABSTRACT
Purpose In order to explore whether TNF-α could regulate C3 expression in tubular epithelial cell which induced renal interstitial fibrosis after unilateral ureteral obstruction, while whether TNF-a receptor antagonist etanercept could reduce C3 expression in renal tubular epithelial cell which could alleviate renal interstitial fibrosis. Methods Wide type (WT) and C3 knock out (C3KO) mice were separately established to set up sham group and UUO group. Moreover, WT UUO mice were intraperitoneal injected with different concentrations of etanercept. Observed TNF-a and C3 expression in operated kidney after UUO in WT mice and C3KO mice, the correlation between TNF-a expression in operated kidney and C3 positive renal tubules, degree of operated kidney renal interstitial fibrosis. Observed TNFR, NF-κB p65, C3 expression in kidney tubular epithelial cell cytomembrane and degree of renal interstitial fibrosis after intraperitoneal injected with different concentrations of etanercept. Results Nearly all of kidney tubular epithelial cells cytomembrane were TNFR positive, some of kidney tubular epithelial cells cytomembrane were C3 positive, operated kidney was TNF-a strongly positive in WT and C3KO mice after UUO, and C3 positive renal tubules were strongly correlated with TNF-α positive cells which were infiltrated in renal insterium. Degree of renal interstitial fibrosis in C3KO UUO mice were alleviated when compared to WT UUO mice (P＜0.01). Expression of C3, NF-κB p65 in kidney tubular epithelial cells were reduced (P＜0.01)and degree of renal interstitial fibrosis were alleviated(P＜0.01)after etanercept treated in WT UUO mice. Conclusion After UUO, TNF-a and C3 were both participated in renal interstitial fibrosis. TNF-a regulated renal tubular epithelial cell C3 expression via renal tubule epithelial cell transcription factor NF-κB p65 which was involved in renal interstitial fibrosis, while the TNF-a receptor antagonism etanercept may block the pathway, and degree of renal interstitial fibrosis pathological changes were alleviated at last.