Correlation of enhanced thrombospondin-1 expression, TGF-β signalling and proteinuria in human type-2 diabetic nephropathy
Hohenstein B, Daniel C, Hausknecht B, Boehmer K, Riess R, Amann KU, Hugo C (2008)
Publication Language: English
Publication Type: Journal article
Publication year: 2008
Journal
Book Volume: 23
Pages Range: 3880-3887
Journal Issue: 12
DOI: 10.1093/ndt/gfn399
Abstract
Background. Activation of the thrombospondin-1 (TSP-1)-TGF-β pathway by glucose and the relevance of TSP-1-dependent activation of TGF-β 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. 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-β 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). Conclusions. In summary, the present study suggests a functional activity of the TSP-1/TGF-β 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-β system as a relevant mechanism for progression of human type-2 diabetic nephropathy. © The Author [2008].
Authors with CRIS profile
Christoph Daniel
Department of Medicine 4 – Nephrology and Hypertension
Kerstin Ute Amann
Professur für Nephropathologie
Involved external institutions
Germany (DE)How to cite
APA:
Hohenstein, B., Daniel, C., Hausknecht, B., Boehmer, K., Riess, R., Amann, K.U., & Hugo, C. (2008). Correlation of enhanced thrombospondin-1 expression, TGF-β signalling and proteinuria in human type-2 diabetic nephropathy. Nephrology Dialysis Transplantation, 23(12), 3880-3887. https://doi.org/10.1093/ndt/gfn399
MLA:
Hohenstein, Bernd, et al. "Correlation of enhanced thrombospondin-1 expression, TGF-β signalling and proteinuria in human type-2 diabetic nephropathy." Nephrology Dialysis Transplantation 23.12 (2008): 3880-3887.
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