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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.
G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
January 2006,
Nephron. Experimental nephrology,
G Wolf, and
E Mueller, and
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F N Ziyadeh
February 1996,
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association,
G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
November 1990,
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G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
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G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
November 2004,
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G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
January 2003,
American journal of nephrology,
G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
July 2003,
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G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
March 1997,
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G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
January 2003,
Nephron. Experimental nephrology,
G Wolf, and
E Mueller, and
R A Stahl, and
F N Ziyadeh
September 2004,
Zhonghua yi xue za zhi,
