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学科主题: 临床医学
题名:
Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury
作者: Sheerin, Neil S.1,2; Risley, Paul1; Abe, Katsu3; Tang, Ziyong1,4; Wong, Wilson1; Lin, Tao1; Sacks, Steven H.1
关键词: proteinuria ; renal failure ; innate immunity
刊名: FASEB JOURNAL
发表日期: 2008-04-01
DOI: 10.1096/fj.07-8719com
卷: 22, 期:4, 页:1065-1072
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
关键词[WOS]: TUBULAR EPITHELIAL-CELLS ; MEMBRANE ATTACK COMPLEX ; EXPERIMENTAL NEPHROTIC SYNDROME ; ADRIAMYCIN NEPHROPATHY ; TUBULOINTERSTITIAL DAMAGE ; ALTERNATIVE PATHWAY ; RENAL-FAILURE ; COMPONENT C3 ; C5B-9 ; PROGRESSION
英文摘要:

Increased exposure of the tubular epithelium to filtered protein is a proposed mechanism of progressive renal failure associated with glomerular disease, but how this protein overload translates into tubular damage remains unclear. We have examined a model of adriamycin-induced proteinuria to determine the effect of locally synthesized C3, the central proinflammatory protein of the complement cascade. C3(-/-) kidney isografts placed in wild-type C3+/+ mice were protected from proteinuria-associated complement activation, tubular damage, and progressive renal failure despite the presence of abundant circulating C3. The quantity of urinary protein was unaffected by the absence of C3, and thus the influence of C3 was not explained by alteration in the filtered protein load. These results suggest that local synthesis of complement from renal epithelial cells is a critical mediator of tubular damage in proteinuria-associated renal disease. Our results concur with previous findings of increased synthesis of C3 in human tubular epithelium exposed to high concentrations of protein in vitro. Because progressive renal damage in humans associates with proteinuria regardless of cause, our findings have implications for the pathogenesis and treatment of renal failure from many common causes, immunological and nonimmunological.

语种: 英语
WOS记录号: WOS:000254581000012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58407
Appears in Collections:北京大学第三临床医学院_肾内科_期刊论文

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作者单位: 1.Kings Coll London, Guys Hosp, Dept Nephrol Transplantat, London WC2R 2LS, England
2.Univ Newcastle Upon Tyne, Sch Med, Sch Clin Med Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
3.Nagasaki Univ, Sch Med, Dept Internal Med 2, Div Nephrol, Nagasaki 852, Japan
4.Peking Univ, Hosp 3, Dept Nephrol, Beijing 100871, Peoples R China

Recommended Citation:
Sheerin, Neil S.,Risley, Paul,Abe, Katsu,et al. Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury[J]. FASEB JOURNAL,2008,22(4):1065-1072.
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