Altered expression of transforming growth factor-beta S in chronic renal rejection.
We examined the altered expression of transforming growth factor-beta s in chronic renal rejection in humans, including transforming growth factor beta-1 (TGF-beta 1), TGF-beta 2, TGF-beta 3 and their receptors, transforming growth factor beta receptor type I (T beta R-I) and T beta R-II. Using Northern blot analysis and immunohistochemistry, 10 specimens of chronically rejected and 8 normal kidney samples were analyzed. By Northern blot analysis the expression of mRNA encoding TGF-beta 1, TGF-beta 2, TGF-beta 3 (P < 0.02), T beta R-I and T beta R-II (P < 0.02) was decreased in chronically rejected renal cortex samples, compared to normal controls. Immunohistochemical analysis of the normal renal cortex showed strong immunostaining for TGF-beta 1 and TGF-beta 3, and mild immunostaining for TGF-beta 2 in the proximal and distal tubulointerstitium, but no signal for any of the TGF-beta isoforms in the glomeruli or in the cortical vessels. In sharp contrast, the glomeruli and the cortical vessels of the rejected kidney specimens exhibited strong immunostaining for TGF-beta 1 and TGF-beta 3, whereas the tubules revealed a decrease in immunoreactivity. T beta RI and T beta RII immunostaining showed similar changes as observed with TGF-beta 1 and TGF-beta 3 antibodies. There was a concomitant increase in B-cell accumulation in the glomeruli, while T-cells and macrophages were diffusely abundant in the rejected samples. Since TGF-beta S are potent inducers of extracellular matrix proteins and have been shown to be involved in fibrotic disease, the increase in TGF-beta 1 and TGF-beta 3 immunoreactivity in the glomeruli suggests that there is a redistribution in TGF-beta expression in chronic renal allograft rejection. Together with changes affected by B-cell mediated immunity, the above alterations might contribute to the histopathological changes that occur in this disorder, such as intimal fibrosis, arteriosclerosis and glomerular and tubular sclerosis.
Horvath
L Z
LZ
Department of Visceral and Transplantation Surgery, University of Berne, Inselspital, Switzerland.
Friess
H
H
Schilling
M
M
Borisch
B
B
Deflorin
J
J
Gold
L I
LI
Korc
M
M
Büchler
M W
MW
D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta