TY - JOUR
T1 - Transforming growth factor beta 2 (TGF-beta2) antagonist attenuates fibrosis in the experimental diabetic rat kidney
AU - Hill, C
AU - Flyvberg, A
AU - Rasch, R
AU - Bak, M
AU - Logan, Ann
PY - 2001/9/1
Y1 - 2001/9/1
N2 - Diabetic nephropathy is characterised by an increase in glomerular and tubular fibrosis that compromises kidney function. The transforming growth factor-betas (TGF-betas) have been shown to play a major role in fibrosis and we have shown that TGF-beta2, in particular, increases coordinately with fibrogenesis in the diabetic kidney. The aim of this study was to investigate the changes in expression of extracellular matrix molecules in the diabetic kidney, with and without systemic administration of a recombinant human monoclonal antibody to TGF-beta2. Streptozotocin-induced diabetic rats were split into two groups. The first were treated with 5 mg/kg irrelevant control IgG4 (placebo) and the second treated with 5 mg/kg isoform-specific recombinant monoclonal anti-TGF-beta2 IgG4 (termed CAT-132) systemically every second day for 14 days. A further group of six non-diabetic rats was also used as a control. Various biological parameters were measured daily throughout the experimental period, and on termination of the experiment at 14 days Western blotting was performed on kidney cortices for procollagen-I C-propeptide, which is an indicator of the rate of collagen-I synthesis,within the kidney. In the placebo-treated diabetic rats, blood glucose, food consumption, urinary albumin excretion (UAE) and kidney weights were all significantly higher than in the non-diabetic group (P
AB - Diabetic nephropathy is characterised by an increase in glomerular and tubular fibrosis that compromises kidney function. The transforming growth factor-betas (TGF-betas) have been shown to play a major role in fibrosis and we have shown that TGF-beta2, in particular, increases coordinately with fibrogenesis in the diabetic kidney. The aim of this study was to investigate the changes in expression of extracellular matrix molecules in the diabetic kidney, with and without systemic administration of a recombinant human monoclonal antibody to TGF-beta2. Streptozotocin-induced diabetic rats were split into two groups. The first were treated with 5 mg/kg irrelevant control IgG4 (placebo) and the second treated with 5 mg/kg isoform-specific recombinant monoclonal anti-TGF-beta2 IgG4 (termed CAT-132) systemically every second day for 14 days. A further group of six non-diabetic rats was also used as a control. Various biological parameters were measured daily throughout the experimental period, and on termination of the experiment at 14 days Western blotting was performed on kidney cortices for procollagen-I C-propeptide, which is an indicator of the rate of collagen-I synthesis,within the kidney. In the placebo-treated diabetic rats, blood glucose, food consumption, urinary albumin excretion (UAE) and kidney weights were all significantly higher than in the non-diabetic group (P
UR - http://www.scopus.com/inward/record.url?scp=0034827951&partnerID=8YFLogxK
U2 - 10.1677/joe.0.1700647
DO - 10.1677/joe.0.1700647
M3 - Article
C2 - 11524245
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
SN - 1479-6805
VL - 170
SP - 647
EP - 651
JO - Journal of Endocrinology
JF - Journal of Endocrinology
IS - 3
ER -