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Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta.
Open accessAbstract
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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Okuda, S., Languino, L. R., Ruoslahti, E., & Border, W. A. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114731 · Cited by 546
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Metadata
- Authors
- Wolf, G., Mueller, E., Stahl, R. A., & Ziyadeh, F. N.
- Venue
- Journal of Clinical Investigation
- Published
- 1993-09-01
- Volume
- 92
- Issue
- 3
- Pages
- 1366-1372
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2107545715
- Cited by
- 379
- References
- 1
- FWCI
- 11.82
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wolf, G., Mueller, E., Stahl, R. A., & Ziyadeh, F. N. (1993). Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta. Journal of Clinical Investigation. https://doi.org/10.1172/jci116710
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