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1 mRNA along rat nephron in
obstructive nephropathy
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Unilateral ureteral obstruction (UUO) leads to
interstitial fibrosis of the obstructed kidney, and transforming growth
factor-
1 (TGF-
1) is thought to play an important role in this
process. Although increased TGF-
1 mRNA expression in the obstructed
kidney has been demonstrated, the source of the increased TGF-
1
remains to be elucidated. To determine the precise localization of
TGF-
1 in the obstructed kidney, we examined TGF-
1 mRNA expression
using in situ hybridization and competitive RT-PCR in rats with UUO. In
situ hybridization demonstrated that TGF-
1 mRNA expression was
preferentially increased in tubular epithelial cells and to a lesser
degree in infiltrating macrophages in obstructed kidneys. Quantitative
analysis using competitive RT-PCR in microdissected nephron segments
revealed that levels of TGF-
1 mRNA in obstructed kidneys relative to
control kidneys increased significantly in proximal tubules, thick
ascending limbs of Henle, and distal convoluted tubules, whereas those
in glomeruli and collecting ducts did not change significantly. Of the
tubular segments, the proximal tubules appeared to predominantly
contribute to increased TGF-
1 mRNA. Our findings suggest that renal
tubules, particularly proximal tubules, are the main contributors to
increased TGF-
1 mRNA expression in obstructed kidneys and to the
subsequent interstitial fibrosis.
unilateral ureteral obstruction; interstitial fibrosis; microdissection; competitive polymerase chain reaction; transforming
growth factor-
1
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