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Apical Proteins Stimulate Complement Synthesis by Cultured Human Proximal Tubular Epithelial Cells

Lookup NU author(s): Professor Neil SheerinORCiD


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There is increasing evidence to suggest that the renal tubular epithelium is important in the pathogenesis of progressive renal failure resulting from persistent proteinuria. The role of complement in the progression of chronic renal failure is not well defined. The purpose of this study was to characterize the production of complement by human proximal tubular epithelial cells exposed to serum proteins at the apical surface. Complement C3 gene expression was analyzed by reverse transcription and PCR. C3 protein biosynthesis was confirmed by metabolic labeling followed by immunoprecipitation and quantified by enzyme-linked immunosorbent assay. In the quiescent state, proximal tubular epithelial cells grown on permeable membrane supports secreted C3 predominantly into the apical medium. The addition of 5 mg/ml serum proteins led to an 8.9-fold increase in basolateral C3 secretion and a 2.1-fold increase in apical C3 secretion, altering the ratio of basolateral: apical C3 secretion from 0.44 +/- 0.16 to 1.87 +/- 0.52. C3 mRNA expression was also upregulated in a time- and dose-dependent manner. Serum fractionation demonstrated that the stimulant responsible for these effects was in the molecular weight range 30 to 100 kD. The observed phenomenon was not reproduced when purified human albumin alone was used as the stimulant. These findings could provide a possible mechanism for the link between proteinuria and interstitial fibrosis. This may have potential implications for strategies directed against complement in retarding the progression of chronic renal failure.

Publication metadata

Author(s): Sheerin NS; Tang S; Zhou W; Brown Z; Sacks SH

Publication type: Article

Publication status: Published

Journal: Journal of the American Society of Nephrology

Year: 1999

Volume: 10

Issue: 1

Pages: 69-76

Print publication date: 01/01/1999

ISSN (print): 1046-6673

ISSN (electronic): 1533-3450

Publisher: American Society of Nephrology


Notes: Journal Article United states Jasn