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Activation of transforming growth factor-beta1 in diabetic kidney disease
B Hellmich1, M Schellner, H Schatz
1Medizinische Klinik und Poliklinik, Abteilung für Endokrinologie, Universitätsklinik Bergmannsheil, Ruhr Universität Bochum, Germany.
Abstract:
Recent data have suggested that certain growth factors and cytokines are involved in the development of diabetic nephropathy. The aim of this study was to investigate whether circulating transforming growth factor beta 1 (TGF-beta1) and tumor necrosis factor alpha (TNF-alpha) are associated with diabetic kidney disease. Serum levels of active and total TGF-beta1 and TNF-alpha were measured in type 2 diabetic patients with nephropathy (n = 23) or without (n = 35) and normoglycemic controls (n = 12). Serum levels of circulating active TGF-beta1 were significantly higher in patients with diabetic nephropathy (0.43 +/- 0.06 ng x mL(-1)) compared with diabetic patients without renal involvement (0.23 +/- 0.03 ng x mL(-1), P = .002) and healthy controls (0.24 +/- 0.03 ng x mL(-1), P= .001), whereas the levels of total (active + latent) TGF-beta1 were not different between the subgroups. Active TGF-beta1 concentrations were correlated with urinary albumin excretion (r = .49, P < .003) and serum creatinine (r= .55, P < .01). Sera from patients with type 2 diabetes contained significantly more TNF-alpha than sera from normoglycemic controls (3.07 +/- 0.24 v 1.65 +/- 0.20 pg x mL(-1), P = .001). However, the comparison of serum TNF-alpha concentrations between microalbuminuric and normoalbuminuric diabetic patients showed no significant difference (3.21 +/- 0.28 v 2.97 +/- 0.34 pg x mL(-1), P = .12). In conclusion, type 2 diabetic patients with diabetic nephropathy exhibit increased activation of TGF-beta1, in serum, suggesting an association between circulating TGF-beta1 activity and the development of renal disease.
Insights
Increased active transforming growth factor beta 1 (TGF-beta1) in serum is linked to diabetic kidney disease in type 2 diabetes patients. This finding suggests TGF-beta1 activation plays a role in developing diabetic nephropathy.
Area of Science:
- Nephrology
- Endocrinology
- Immunology
Background:
- Diabetic nephropathy is a major complication of type 2 diabetes.
- Growth factors and cytokines are implicated in its development.
- Circulating biomarkers are needed for early detection and understanding pathogenesis.
Purpose of the Study:
- To investigate the association between serum levels of transforming growth factor beta 1 (TGF-beta1) and tumor necrosis factor alpha (TNF-alpha) and diabetic kidney disease in type 2 diabetes.
- To determine if active or total TGF-beta1 and TNF-alpha levels differ in patients with and without diabetic nephropathy.
Main Methods:
- Serum samples were collected from type 2 diabetic patients with nephropathy (n=23), without nephropathy (n=35), and normoglycemic controls (n=12).
- Levels of active and total TGF-beta1 and TNF-alpha were measured using immunoassays.
- Statistical analyses were performed to compare groups and assess correlations.
Main Results:
- Serum levels of active TGF-beta1 were significantly higher in diabetic nephropathy patients compared to diabetic patients without nephropathy and healthy controls (P=.002 and P=.001, respectively).
- Active TGF-beta1 concentrations correlated positively with urinary albumin excretion (r=.49) and serum creatinine (r=.55).
- Serum TNF-alpha levels were higher in all type 2 diabetic patients compared to controls (P=.001), but no significant difference was found between microalbuminuric and normoalbuminuric diabetic patients.
Conclusions:
- Type 2 diabetic patients with diabetic nephropathy show increased serum active TGF-beta1.
- Circulating active TGF-beta1 activity is associated with the development of diabetic kidney disease.
- While TNF-alpha is elevated in diabetes, its specific role in nephropathy progression in this study was not clearly defined.