Essential role(s) of the intrarenal renin-angiotensin system in transforming growth factor-beta1 gene expression and induction of hypertrophy of rat kidney proximal tubular cells in high glucose.

Published

Journal Article

These studies investigated the question of whether the intrarenal renin-angiotensin system (RAS) is essential for transforming growth factor-beta1 (TGF-beta1) gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose in vitro. Antisense and sense angiotensinogen (ANG) cDNAs were stably transfected into rat immortalized renal proximal tubular cells (IRPTC). ANG secretion from rat IRPTC was quantified by a specific RIA for rat ANG. Cellular ANG, TGF-beta1, and collagen alpha1 (type IV) mRNA levels were determined by Northern blot analysis or by reverse transcriptase-PCR assay. Hypertrophy of IRPTC was analyzed by Western blotting of cellular p27(Kip1) protein, flow cytometry, and cellular protein assay. The results showed that stable transfer of antisense ANG cDNA into IRPTC suppressed the basal TGF-beta1 and collagen alpha1 (type IV) mRNA expression and blocked the stimulatory effect of high glucose (i.e., 25 mM) on TGF-beta1 and collagen alpha1 (type IV) mRNA expression and induction of IRPTC hypertrophy. In contrast, stable transfer of sense ANG cDNA into IRPTC had no significant effect on these parameters. These data demonstrate that local intrarenal RAS activation is essential for TGF-beta1 gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose.

Full Text

Duke Authors

Cited Authors

  • Zhang, S-L; To, C; Chen, X; Filep, JG; Tang, S-S; Ingelfinger, JR; Chan, JSD

Published Date

  • February 2002

Published In

Volume / Issue

  • 13 / 2

Start / End Page

  • 302 - 312

PubMed ID

  • 11805157

Pubmed Central ID

  • 11805157

International Standard Serial Number (ISSN)

  • 1046-6673

Language

  • eng

Conference Location

  • United States