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《Immunological Journal》 2015-05
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Effects of albumin overload on C3a-C3aR signaling pathway and IL-17 expression in adriamycin nephropathy mice

WEI Xinyi;XIAO Lei;YANG Baohui;YANG Haiping;LI Qiu;Ministry of Education Key Laboratory of Child Development and Disorders & Key Laboratory of Pediatrics in Chongqing & Chongqing International Science and Technology Cooperation Center for Child Development and Disorders;Department of Nephrology and Immunology,Children's Hospital of Chongqing Medical University;  
Proteinuria is a proposed mechanism of progressive renal failure associated with glomerular disease.This study designed to observe the effects of albumin overload on C3a-C3 a R signaling pathway and IL-17 expression in adriamycin nephropathy(ADR) mice, and initially explore immunological mechanism of albumin overload-caused kidney damage. SPF healthy male Balb/c mice were randomly divided into control group, ADR group, and ADR with bovine serum albumin overload(ADR+BSA) group. All mice were uninephrectomized under general anesthesia 2 weeks before setting up ADR model. At the end of the 6thweek, ADR +BSA group received weekly 5 intraperitoneally injections of low endotoxin BSA at a dose of 10 mg/g body weight for 4 weeks. At the end of 6thand 10 thweek, 24 hours urinary protein, serum biochemical indexes and kidney pathological changes were evaluated. Expression levels of C3 a, C3 a R and TGF-β1 in kidney was measured by real-time PCR and immunohistochemistry; expression of IL-17 in kidney was measured by ELISA and immunohistochemistry. We found that expression levels of C3 a, C3 a R, TGF-β1 and IL-17 in ADR group were higher than those in control group(P 0.05). At the end of 10 thweek, ADR +BSA group appeared proteinuria and BUN increasing(P 0.001).Under electronic microscope, we observed glomerular sclerosis of focal segmental and renal tubular damage.Expression levels of C3 a, C3 a R, TGF-β1 and IL-17 in ADR+BSA group were higher than those in control and ADR group(P 0.05). In conclusion, activation of C3aC3 a R signaling pathway exists in adriamycin nephropathy mice. Albumin overload can produce much proteinuria, which could accelerate the progressive kidney damage. Proteinuria activating theexpression of C3a-C3 a R signaling pathway, TGF-β1 and IL-17 in adriamycin nephropathy mice might be the potential mechanism.
【Fund】: 国家自然科学基金面上项目(81270802;81070563);国家自然科学基金青年科学基金项目(81200520)
【CateGory Index】: R726.9
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