Thrombospondin 1 precedes and predicts the development of tubulointerstitial fibrosis in glomerular disease in the rat.

Abstract:

:Tubulointerstitial fibrosis is one of the most important histologic features that predicts progression in kidney disease. Thrombospondin 1 is an extracellular matrix protein that can activate latent TGF-beta, a cytokine implicated in the pathogenesis of tubulointerstitial fibrosis. We examined the expression of thrombospondin 1 in several animal models of glomerulonephritis (anti-Thy1 model, aminonucleoside nephrosis, passive Heymann nephritis) that are associated with tubulointerstitial disease. Thrombospondin 1 mRNA and protein were transiently increased in tubular cells, myofibroblasts and some macrophages in areas of tubulointerstitial injury. Thrombospondin 1 expression always preceded the development of tubulointerstitial fibrosis, and correlated quantitatively and spatially with the later development of interstitial fibrosis. Thrombospondin 1 expression predicted the severity of tubulointerstitial fibrosis better than the degree of macrophage or myofibroblast accumulation. Thrombospondin 1 expression was associated with increased expression and activation of TGF-beta1 and decreased expression of LAP-TGF-beta in areas of tubulointerstitial injury. We conclude that thrombospondin 1 is an early marker predicting the development of tubulointerstitial kidney disease. De novo expression of thrombospondin 1 is associated and colocalized with increased expression of TGF-beta1 and decreased expression of LAP-TGF-beta during the development of tubulointerstitial disease in vivo. These data are consistent with the possibility that thrombospondin 1 may be an endogenous activator of TGF-beta.

journal_name

Kidney Int

journal_title

Kidney international

authors

Hugo C,Shankland SJ,Pichler RH,Couser WG,Johnson RJ

doi

10.1046/j.1523-1755.1998.00774.x

subject

Has Abstract

pub_date

1998-02-01 00:00:00

pages

302-11

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)60398-2

journal_volume

53

pub_type

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