Altered expression of transforming growth factor-βs in chronic renal rejection

Laszlo Zs Horvath, Helmut Friess, Martin Schilling, Bettina Borisch, Judith Deflorin, Leslie I. Gold, Murray Korc, Markus W. Büchler

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47 Scopus citations

Abstract

We examined the altered expression of transforming growth factor-βs in chronic renal rejection in humans, including transforming growth factor beta-1 (TGF-β1), TGF-β2, TGF-β3 and their receptors, transforming growth factor beta receptor type I (TβR-I) and TβR-II. Using Northern blot analysis and immunohistochemistry, 10 specimens of chronically rejected and g normal kidney samples were analyzed. By Northern blot analysis the expression of mRNA encoding TGF-β1, TGF-β2, TGF-β3 (P < 0.02), TβR-I and TβR-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-β1 and TGF-β3, and mild immunostaining for TGF-β2 in the proximal and distal tubulointerstitium, but no signal for any of the TGF-β 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-β1 and TGF-β3, whereas the tubules revealed a decrease in immunoreactivity. TβRI and TβRII immunostaining showed similar changes as observed with TGF-β1 and TGF-β3 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- βs are potent inducers of extracellular matrix proteins and have been shown to be involved in fibrotic disease, the increase in TGF-β1 and TGF-β3 immunoreactivity in the glomeruli suggests that there is a redistribution in TGF-β 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.

Original languageEnglish (US)
Pages (from-to)489-498
Number of pages10
JournalKidney international
Volume50
Issue number2
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Nephrology

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    Horvath, L. Z., Friess, H., Schilling, M., Borisch, B., Deflorin, J., Gold, L. I., Korc, M., & Büchler, M. W. (1996). Altered expression of transforming growth factor-βs in chronic renal rejection. Kidney international, 50(2), 489-498. https://doi.org/10.1038/ki.1996.340