Increased transforming growth factor-beta1 and tubulointerstitial fibrosis in rats with congenital hydronephrosis.
OBJECTIVE
Most of our knowledge concerning renal obstruction has been derived from experimental animal models, and it is not yet well defined in spontaneous hydronephrosis. The aim of our study is to evaluate the roles of transforming growth factor-beta1 (TGF-beta1) and apoptosis in congenital hydronephrotic kidneys in comparison with experimental models.


METHODS
We made histological studies on kidneys from 6-week-old Wistar-Imamichi rats with congenital unilateral hydronephrosis as well as surgical models of complete or partial unilateral ureteral obstruction. The severity of hydronephrotic kidneys was evaluated on routine hematoxylin and eosin (H&E) stained sections, and the tubulointerstitial fibrosis analyzed morphometrically on Masson's trichrome stained sections. Renal tubular atrophy was assessed on periodic acid Schiff (PAS) stained sections, and tubular cell apoptosis assessed with TUNEL technique. The renal TGF-beta1 level was determined by a sandwich enzyme-linked immunosorbent assay (ELISA).


RESULTS
We observed a significant loss of kidney weight with profound compensatory growth of the contralateral kidney in rats with congenital hydronephrosis. Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, renal parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. The renal TGF-beta1 level was markedly elevated in hydronephrotic kidneys as compared with normal controls (326.01 +/- 30.64 pg/mg protein vs 227.81 +/- 11.07 pg/mg protein, P < 0.01). The tubular apoptotic score in hydronephrotic kidneys was also significantly higher than normal controls (2.17 +/- 0.50/HPF [high power field]vs 0.14 +/- 0.04/HPF, P < 0.01). The increased TGF-beta1 and apoptotic status paralleled the histological changes of tubulointerstitial fibrosis and tubular atrophy. Similar findings were also obtained in experimental obstructive models.


CONCLUSIONS
In comparison with surgical models of partial and complete ureteral obstruction, our data provide solid morphological and molecular evidences of renal obstruction in rats with congenital hydronephrosis.
Zhou
Yun
Y
Department of Urology, St Marianna University School of Medicine, Kawasaki, Japan. goh@marianna-u.ac.jp
Takahashi
Go
G
Shinagawa
Toshihito
T
Okuhara
Toshini
T
Yonamine
Kyoko
K
Aida
Yoshio
Y
Tadokoro
Mamoru
M
D000818:Animals; D005355:Fibrosis; D006869:Hydronephrosis / Q000150:complications / Q000151:congenital* / Q000378:metabolism*; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1