EXPERIMENTAL BILATERAL URINARY OBSTRUCTION IN FETAL SHEEP - TRANSFORMING GROWTH-FACTOR-BETA-1 EXPRESSION

To gain insight into the role of transforming growth factor-beta 1 (TG F-beta 1) in the development of kidney pathology following fetal obstr uction, we measured TGF-beta 1 gene expression, the active peptide, an d the urinary concentration in a model of fetal bilateral urinary obst ruction (BUG) in sheep. Fetal lambs underwent BUO at 60 (FO-60) or 80 days (FO-80) of gestation and were studied at 120 days. Independently of the onset or duration of obstruction, all fetuses developed type IV dysplasia (TV) associated with an arrest in the nephrogenesis or hydr onephrosis. Fetal glomerular filtration rate was not significantly mod ified, whereas sodium tubular reabsorption was significantly decreased , and urinary TGF-beta 1 concentration was elevated in hydronephrosis but not in IV. Levels of TGF-beta 1 mRNA were increased in hydronephro sis compared with normal kidneys, and active TGF-beta 1 immunoreactivi ty was increased in both hydronephrotic and IV kidneys. In summary, TG F-beta 1 may play a role in the development of hydronephrosis and dysp lasia in kidneys following fetal BUO. Its role in the arrest of nephro genesis observed in the IV kidneys remains to be proved.