Nephrology Dialysis Transplantation, Vol 13, Issue 7 1668-1674, Copyright © 1998 by Oxford University Press
M Rastaldi, S Tunesi, F Ferrario, A Indaco, H Zou, P Napodano and G D'Amico
Background: Among our cases of IgA glomerulonephritis
(IgAGN), 10% show necrotizing/extracapillary lesions involving a small
percentage of glomeruli and associated with a ceratin degree of
inflammation in absence of glomerular and interstitial scarring. In our
experience, also in repeat biopsies, these cases of IgAGN have a worse
prognosis probably because necrotizing/extracapillary lesions can repeat
and accumulate, leading to the progression of damage. As it is well known
that transforming growth factor-{beta} (TGF-{beta}) and endothelin-1
(ET-1) are key-factors in the progression of glomerulonephritis, aim of the
study was to examine their expression in renal biopsies of primary IgAGN
with necrotizing/crescentic lesions in complete absence of interstitial
fibrosis. To obtain information about the mitogenic effect of ET-1, the
expression of c-fos, whose upregulation by ET-1 has
been established in culture, was also studied.
Methods: Eighteen renal biopsies of patients with
necrotizing/crescentic IgAGN were examined by immunohistochemistry with
antibodies against TGF-{beta}, ET-1 and c-fos. The
results were compared with those obtained on 22 cases of IgAGN
characterized only by pure mesangial proliferation and 25 IgAGN biopsies
with advanced, not active, glomerulointerstitial lesions.
Results: In necrotizing/crescentic IgAGN glomerular
TGF-{beta} appeared more positive than in cases characterized only by
pure mesangial proliferation and was especially expressed on cellular
crescents. In the interstitium, TGF-{beta}, ET-1 and
c-fos were expressed by infiltrating leukocytes,
tubules, and small vessels. This positivity, although similar as
localization, was less diffuse than in biopsies with advanced interstitial
damage, but significantly greater than in cases with pure mesangial
proliferation. Conclusions: Positivity of
TGF-{beta} on cellular crescents is similar to that observed from other
authors in different types of necrotizing/crescentic human
glomerulonephritis and supports our hypothesis that this is a peculiar type
of IgAGN. Moreover, interstitial expression of TGF-{beta}, ET-1 and
c-fos in biopsies with glomerular active lesions but
complete absence of interstitial fibrosis may potentially represent a
signal of activation of mechanisms that induce and amplify the damage
leading to further progression of the disease. Key words:
c-fos; ET-1; immunohistochemistry; necrotizing/crescentic IgAGN;
TGF-{beta}
ORIGINAL ARTICLES
Transforming growth factor-{beta}, endothelin-1, and c-fos expression in necrotizing/crescentic IgA glomerulonephritis
Division of Nephrology, San Carlo Borromeo Hospital, Via Pio II, 3, 220153 Milano, Italy; Corresponding author
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