Korean J Urol.  1996 May;37(5):493-504.

Evolution and Regulation of Renal Renin and Transforming Growth Factor beta 1 Gene Expression in the Unilateral Ureteral Obstruction of the Neonatal Rat

• Chung KH
• Choi H

Abstract

Unilateral ureteral obstruction(UUO) in early development impairs renal growth. To investigate the potential role of growth-related peptides in this response, Sprague-Dawley rats underwent UUO or sham operation in the first 48 hours of life, and kidneys were harvested 1 to 14 days later. Renal mRNA was quantitated by Northern and dot blot with complementary DNA probes for renin and transforming growth factor beta 1(TGF-beta1). Renin distribution was determined by immunohistochemistry. Adult rats were also studied 3 or 14 days after UUO or sham operation. Unlike the neonate, in which renal DNA failed to increase with chronic ipsilateral UUO, renal DNA increased in the adult. UUO increased renal renin mRNA and protein distribution in the neonate,but mRNA expression did not change in the adult.TGF-beta1 expression increased in the obstructed kidney in both neonates and adults. Since renal renin expression is increased by UUO, it was hypothesized that by activation of angiotensin II type 1 receptor, angiotensin II regulates expression of TGF-beta1 in the obstructed kidney. Sprague-Dawley rats underwent left UUO or sham operation within the first 48 hours of life, and received losartan or saline. After 14 days, steady-state renal mRNA was determined for renin and TGF-beta1. Losartan reduced the DNA content of the intact kidneys, but did not further decrease that of the obstructed kidney. Losartan increased renal renin expression regardless of UUO. In contrast, losartan reduced TGF-beta1 expression by 34% in obstructed kidneys, but did not affect TGF-beta1 in intact kidneys. In conclusion, neonatal UUO delays renal maturation, possibly related to altered renin and TGF-beta1 expression and activation of the angiotensin II type 1 receptor is necessary for normal renal growth, and TGF-beta1 is regulated by angiotensin II type 1 receptor in the obstructed, but not intact kidneys.

Keyword

unilateral ureteral obstruction; renin

MeSH Terms

Adult
Angiotensin II
Animals
DNA
DNA, Complementary
Humans
Immunohistochemistry
Infant, Newborn
Kidney
Losartan
Peptides
Rats*
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Renin*
RNA, Messenger
Transforming Growth Factor beta*
Transforming Growth Factor beta1
Transforming Growth Factors*
Ureter*
Ureteral Obstruction*
Angiotensin II
DNA
DNA, Complementary
Losartan
Peptides
RNA, Messenger
Receptor, Angiotensin, Type 1
Renin
Transforming Growth Factor beta
Transforming Growth Factor beta1
Transforming Growth Factors