TY - JOUR
T1 - Cellular basis of diabetic nephropathy
T2 - II. The transforming growth factor-β system and diabetic nephropathy lesions in type 1 diabetes
AU - Huang, Chunmei
AU - Kim, Youngki
AU - Caramori, Maria Luiza A.
AU - Fish, Alfred J.
AU - Rich, Stephen S.
AU - Miller, Michael E.
AU - Russell, Gregory B.
AU - Mauer, Michael
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Transforming growth factor-β (TGF-β) may be critical in the development of diabetic nephropathy (DN), and genetic predisposition is an important determinant of DN risk. We evaluated mRNA expression levels of TGF-β system components in cultured skin fibroblasts (SFs) from type 1 diabetic patients with fast versus slow development of DN. A total of 125 long-standing type 1 diabetic patients were ranked by renal mesangial expansion score (MES) based on renal biopsy findings and diabetes duration. Patients in the highest quintile of MES who were also microalbuminuric or proteinuric (n = 16) were classified as "fast-track" for DN, while those in the lowest quintile who were also normoalbuminuric (n = 23) were classsified as "slow-track" for DN. Twenty-five normal subjects served as control subjects. SFs were cultured in medium with 25 mmol/l glucose for 36 h. SF mRNA expression levels for TGF-β1, TGF-β type II receptor (TGF-β RII), thrombospondin-1, and latent TGF-β binding protein-1 (LTBP-1) were measured by real-time RT-PCR. LTBP-1 mRNA expression was reduced in slow-track (0.99 ± 0.38) versus fast-track patients (1.65 ± 0.52, P = 0.001) and control subjects (1.41 ± 0.7, P = 0.025). mRNA levels for TGF->1, TGF-> RII, and thrombospondin-1 were similar in the three groups. Reduced LTBP-1 mRNA expression in SFs from slow-track patients may reflect genetically determined DN protection and suggests that LTBP-1 may be involved in the pathogenesis of DN through the regulation of TGF-> activity.
AB - Transforming growth factor-β (TGF-β) may be critical in the development of diabetic nephropathy (DN), and genetic predisposition is an important determinant of DN risk. We evaluated mRNA expression levels of TGF-β system components in cultured skin fibroblasts (SFs) from type 1 diabetic patients with fast versus slow development of DN. A total of 125 long-standing type 1 diabetic patients were ranked by renal mesangial expansion score (MES) based on renal biopsy findings and diabetes duration. Patients in the highest quintile of MES who were also microalbuminuric or proteinuric (n = 16) were classified as "fast-track" for DN, while those in the lowest quintile who were also normoalbuminuric (n = 23) were classsified as "slow-track" for DN. Twenty-five normal subjects served as control subjects. SFs were cultured in medium with 25 mmol/l glucose for 36 h. SF mRNA expression levels for TGF-β1, TGF-β type II receptor (TGF-β RII), thrombospondin-1, and latent TGF-β binding protein-1 (LTBP-1) were measured by real-time RT-PCR. LTBP-1 mRNA expression was reduced in slow-track (0.99 ± 0.38) versus fast-track patients (1.65 ± 0.52, P = 0.001) and control subjects (1.41 ± 0.7, P = 0.025). mRNA levels for TGF->1, TGF-> RII, and thrombospondin-1 were similar in the three groups. Reduced LTBP-1 mRNA expression in SFs from slow-track patients may reflect genetically determined DN protection and suggests that LTBP-1 may be involved in the pathogenesis of DN through the regulation of TGF-> activity.
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U2 - 10.2337/diabetes.51.12.3577
DO - 10.2337/diabetes.51.12.3577
M3 - Article
C2 - 12453917
AN - SCOPUS:0036895640
SN - 0012-1797
VL - 51
SP - 3577
EP - 3581
JO - Diabetes
JF - Diabetes
IS - 12
ER -
