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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.
- 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.
- Subjects :
- Adult
Aged
Case-Control Studies
Diabetes Mellitus, Type 2 pathology
Diabetic Nephropathies pathology
Fibrosis
Humans
Middle Aged
Proteinuria physiopathology
Signal Transduction
Smad2 Protein metabolism
Smad3 Protein metabolism
Diabetes Mellitus, Type 2 physiopathology
Diabetic Nephropathies physiopathology
Thrombospondin 1 metabolism
Transforming Growth Factor beta metabolism
Subjects
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