Jl. Pimentel et al., ROLE OF ANGIOTENSIN-II IN THE EXPRESSION AND REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA IN OBSTRUCTIVE NEPHROPATHY, Kidney international, 48(4), 1995, pp. 1233-1246
Unilateral ureteral obstruction (UUO) leads to fibrosis of the obstruc
ted kidney. We tested the hypothesis that interstitial fibrosis in UUO
results, at least in part, from enhanced expression of transforming g
rowth factor-beta (TGF-beta) which in turn is regulated by local angio
tensin II (Ang II) generation. (The generic name TGF-beta is used to d
iscuss properties shared by all isoforms, but special reference to oth
er isoforms is made when specifically needed.) Using Northern blot and
immunohistochemical analysis, we examined the expression of TGF-beta
in rat kidneys after 24 hours (aUUO) and one week (cUUO) of obstructio
n. Obstructed kidneys from both periods had increased interstitial and
perivascular TGF-beta immunoreactivity compared to contralateral and
sham kidneys, in which immunostaining was confined to the inner medull
a. Relative abundance of all TGF-beta mRNA isoforms were higher in the
obstructed than in contralateral and sham kidneys in both aUUO and cU
UO. Expression of TGF-beta isoforms varied according to site (cortex v
s. medulla), segment of the nephron, type of cells and duration of the
obstruction. The increase in TGF-beta immunoreactivity and mRNA level
s in aUUO and cUUO was almost totally abolished by pretreatment with l
osartan. We conclude that in UUO: (a) TGF-beta gene expression is incr
eased and differentially regulated; (b) Ang II, at least partially, me
diates the overexpression of TGF-beta gene; and (c) Ang II may play a
central role in fibrogenesis in this and other models of tubulointerst
itial disease.