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Correlation of enhanced thrombospondin-1 expression, TGF-beta signalling and proteinuria in human type-2 diabetic nephropathy.

Correlation of enhanced thrombospondin-1 expression, TGF-beta signalling and proteinuria in human type-2 diabetic nephropathy.

Authors :
Hohenstein B
Daniel C
Hausknecht B
Boehmer K
Riess R
Amann KU
Hugo CP
Source :
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2008 Dec; Vol. 23 (12), pp. 3880-7. Date of Electronic Publication: 2008 Jul 30.
Publication Year :
2008

Abstract

Background: Activation of the thrombospondin-1 (TSP-1)-TGF-beta pathway by glucose and the relevance of TSP-1-dependent activation of TGF-beta for renal matrix expansion, renal fibrosis and sclerosis have previously been demonstrated by our group in in vivo and in vitro studies. Design and methods. We investigated renal biopsies (n = 40) and clinical data (n = 30) of patients with diabetic nephropathy. Ten kidneys without evidence of renal disease served as controls. Glomerular and cortical expression of TSP-1, p-smad2/3, fibrosis and glomerular sclerosis (PAS) were assessed by immunhistochemical staining and related with clinical data.<br />Results: Glomerular (g) and cortical (c) TSP-1 were increased during diabetic nephropathy (g: 2.62 +/- 2.65; c: 4.5 +/- 4.2) compared to controls (g: 0.67 +/- 0.7; c: 1.5 +/- 1.2). P-smad2/3 was significantly increased (g: 16.7 +/- 12.9; c: 148.7 +/- 92.8) compared to controls (g: 7.1 +/- 3.6; c: 55 +/- 25; P < 0.05). TSP-1 was coexpressed with p-smad2/3 as an indicator of TGF-beta activation. TSP-1 correlated with enhanced tubulointerstitial p-smad2/3 positivity (r = 0.39 and r = 0.4, P < 0.05) and glomerular p-smad2/3 correlated with proteinuria (r = 0.35, P < 0.05).<br />Conclusions: In summary, the present study suggests a functional activity of the TSP-1/TGF-beta axis, especially in the tubulointerstitium of patients with diabetic nephropathy. The positive correlation of glomerular p-smad2/3 positivity with proteinuria further supports the importance of the TSP-1/TGF-beta system as a relevant mechanism for progression of human type-2 diabetic nephropathy.

Details

Language :
English
ISSN :
1460-2385
Volume :
23
Issue :
12
Database :
MEDLINE
Journal :
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Publication Type :
Academic Journal
Accession number :
18676351
Full Text :
https://doi.org/10.1093/ndt/gfn399