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Am J Physiol Renal Physiol 264: F996-F1002, 1993;
0363-6127/93 $5.00
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AJP - Renal Physiology, Vol 264, Issue 6 996-1002, Copyright © 1993 by American Physiological Society


ARTICLES

Metanephric transforming growth factor-beta 1 regulates nephrogenesis in vitro

S. A. Rogers, G. Ryan, A. F. Purchio and M. R. Hammerman
George M. O'Brien Kidney and Urological Diseases Center, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.

Development of the metanephric kidney during embryogenesis is regulated by a number of polypeptide growth factors of renal origin. We have defined previously a role for insulin-like growth factors (IGF) I and II and for transforming growth factor (TGF)-alpha. To delineate the effect of TGF-beta 1, on renal organogenesis, we cultured metanephroi surgically dissected from 13-day-old rat embryos in serum-free chemically defined media. TGF-beta 1 mRNA was present in kidneys from 13-day-old rat embryos, and positive immunostaining for TGF-beta 1 could be demonstrated in cultured metanephroi. However, TGF-beta bioactivity could not be detected in media obtained from the metanephroi. Addition of 10(-9) M TGF-beta 1 to cultures inhibited tubulogenesis, but had no effect on synthesis of IGF-I or -II. Addition of anti-TGF-beta 1 antibodies to cultures accelerated tubulogenesis within the metanephric blastema. These findings establish the potential for TGF-beta 1 production within the rat metanephros during development in vivo. It is possible that this peptide exerts a negative control on the process of tubulogenesis within metanephric blastema and in this manner acts to shape the architecture of mature kidney.


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