Cellular basis of diabetic nephropathy

II. The transforming growth factor-β system and diabetic nephropathy lesions in type 1 diabetes

Chunmei Huang, Youngki Kim, Maria Luiza A. Caramori, Alfred J. Fish, Stephen S. Rich, Michael E. Miller, Gregory B. Russell, Michael Mauer

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3577-3581
Number of pages5
JournalDiabetes
Volume51
Issue number12
DOIs
StatePublished - Dec 1 2002

Fingerprint

Diabetic Nephropathies
Transforming Growth Factors
Type 1 Diabetes Mellitus
Carrier Proteins
Messenger RNA
Fibroblasts
Thrombospondin 1
Skin
Kidney
Growth Factor Receptors
Genetic Predisposition to Disease
Real-Time Polymerase Chain Reaction
Biopsy
Glucose

Cite this

Cellular basis of diabetic nephropathy : II. The transforming growth factor-β system and diabetic nephropathy lesions in type 1 diabetes. / Huang, Chunmei; Kim, Youngki; Caramori, Maria Luiza A.; Fish, Alfred J.; Rich, Stephen S.; Miller, Michael E.; Russell, Gregory B.; Mauer, Michael.

In: Diabetes, Vol. 51, No. 12, 01.12.2002, p. 3577-3581.

Research output: Contribution to journalArticle

Huang, Chunmei ; Kim, Youngki ; Caramori, Maria Luiza A. ; Fish, Alfred J. ; Rich, Stephen S. ; Miller, Michael E. ; Russell, Gregory B. ; Mauer, Michael. / Cellular basis of diabetic nephropathy : II. The transforming growth factor-β system and diabetic nephropathy lesions in type 1 diabetes. In: Diabetes. 2002 ; Vol. 51, No. 12. pp. 3577-3581.
@article{b01df7ea9368483d96b4eb52a4fab644,
title = "Cellular basis of diabetic nephropathy: II. The transforming growth factor-β system and diabetic nephropathy lesions in type 1 diabetes",
abstract = "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.",
author = "Chunmei Huang and Youngki Kim and Caramori, {Maria Luiza A.} and Fish, {Alfred J.} and Rich, {Stephen S.} and Miller, {Michael E.} and Russell, {Gregory B.} and Michael Mauer",
year = "2002",
month = "12",
day = "1",
doi = "10.2337/diabetes.51.12.3577",
language = "English (US)",
volume = "51",
pages = "3577--3581",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "12",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0036895640&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036895640&partnerID=8YFLogxK

U2 - 10.2337/diabetes.51.12.3577

DO - 10.2337/diabetes.51.12.3577

M3 - Article

VL - 51

SP - 3577

EP - 3581

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 12

ER -