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Research Article Free access | 10.1172/JCI116710

Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta.

G Wolf, E Mueller, R A Stahl, and F N Ziyadeh

Department of Medicine, University of Frankfurt, Germany.

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Department of Medicine, University of Frankfurt, Germany.

Find articles by Mueller, E. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Frankfurt, Germany.

Find articles by Stahl, R. in: JCI | PubMed | Google Scholar

Department of Medicine, University of Frankfurt, Germany.

Find articles by Ziyadeh, F. in: JCI | PubMed | Google Scholar

Published September 1, 1993 - More info

Published in Volume 92, Issue 3 on September 1, 1993
J Clin Invest. 1993;92(3):1366–1372. https://doi.org/10.1172/JCI116710.
© 1993 The American Society for Clinical Investigation
Published September 1, 1993 - Version history
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Abstract

Previous studies by our group have demonstrated that angiotensin II (ANG II), as a single factor in serum-free medium, induces cellular hypertrophy of a cultured murine proximal tubular cell line (MCT). The present study was performed to test the hypothesis that this growth effect was mediated by activation of endogenous transforming growth factor-beta (TGF-beta). Exogenous TGF-beta 1 (1 ng/ml) mimicked the growth effects observed with 10(-8) M ANG II (inhibition of DNA synthesis and induction of cellular hypertrophy). A neutralizing anti-TGF-beta antibody attenuated the ANG II-induced increase in de novo protein and total RNA synthesis as well as total protein content. This antibody also abolished the ANG II-mediated inhibition of [3H]thymidine incorporation into quiescent MCT cells. Control IgG or an unrelated antibody had no effect. A bioassay for TGF-beta using mink lung epithelial cells revealed that MCT cells treated with ANG II released active TGF-beta into the cell culture supernatant. Northern blot analysis and semi-quantitative cDNA amplification demonstrated increases in steady-state levels for TGF-beta 1 mRNA after ANG II stimulation of MCT cells, but not in a syngeneic murine mesangial cell line. Our data indicate that the ANG II-induced hypertrophy in MCT cells is mediated by synthesis and activation of endogenous TGF-beta. It is intriguing to speculate that TGF-beta may play a role in the early tubular cell hypertrophy and the subsequent interstitial scarring observed in several models of chronic renal injury that are characterized by increased activity of intrarenal ANG II.

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