Hyperglycemia and diabetic kidney disease: The case for transforming growth factor-β as a key mediator

Kumar Sharma, F. N. Ziyadeh

Research output: Contribution to journalReview article

518 Citations (Scopus)

Abstract

Renal cells are a rich source of transforming growth factor (TGF)-β, and they serve as targets for its actions. Our hypothesis that activation of the TGF-β system in the kidney is implicated in the development of diabetic renal disease stems from the close similarity of actions of TGF-β and high ambient glucose on renal cell growth and extracellular matrix metabolism. Proximal tubule cells and glomerular mesangial cells cultured in high glucose concentration express increased TGF-β1 mRNA and protein levels, and treatment with anti-TGF-β antibodies results in prevention of the effects of high glucose to induce cellular hypertrophy and stimulate collagen biosynthesis. Several in vive studies by different groups of investigators have reported overexpression of TGF-β in the glomeruli in human and experimental diabetes. We have also observed that the development of renal hypertrophy in the insulin-dependent diabetic BB rat and NOD mouse is associated with increased expression of TGF-β1 in the kidney and that short- term administration of antibodies capable of neutralizing the activity of TGF-β in the streptozotocin mouse model of diabetes results in attenuation of whole kidney and glomerular hypertrophy and overexpression of mRNAs encoding matrix components. Together, these findings are consistent with the hypothesis that the diabetic state stimulates TGF-β expression in the kidney and that in turn this growth factor may mediate, in an autocrine/paracrine manner, some of the principal early manifestations of diabetic renal disease. Demonstrating a causal link between upregulation of glomerular TGF-β and the subsequent development of diabetic glomerulosclerosis will require long-term interventional studies designed to intercept the TGF-β system in the kidney.

Original languageEnglish (US)
Pages (from-to)1139-1146
Number of pages8
JournalDiabetes
Volume44
Issue number10
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Diabetic Nephropathies
Transforming Growth Factors
Hyperglycemia
Kidney
Hypertrophy
Glucose
Inbred BB Rats
Messenger RNA
Inbred NOD Mouse
Mesangial Cells
Streptozocin
Neutralizing Antibodies
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Up-Regulation
Collagen
Research Personnel
Insulin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Hyperglycemia and diabetic kidney disease : The case for transforming growth factor-β as a key mediator. / Sharma, Kumar; Ziyadeh, F. N.

In: Diabetes, Vol. 44, No. 10, 01.01.1995, p. 1139-1146.

Research output: Contribution to journalReview article

@article{0acfc61a19654832b7622ed7698c9240,
title = "Hyperglycemia and diabetic kidney disease: The case for transforming growth factor-β as a key mediator",
abstract = "Renal cells are a rich source of transforming growth factor (TGF)-β, and they serve as targets for its actions. Our hypothesis that activation of the TGF-β system in the kidney is implicated in the development of diabetic renal disease stems from the close similarity of actions of TGF-β and high ambient glucose on renal cell growth and extracellular matrix metabolism. Proximal tubule cells and glomerular mesangial cells cultured in high glucose concentration express increased TGF-β1 mRNA and protein levels, and treatment with anti-TGF-β antibodies results in prevention of the effects of high glucose to induce cellular hypertrophy and stimulate collagen biosynthesis. Several in vive studies by different groups of investigators have reported overexpression of TGF-β in the glomeruli in human and experimental diabetes. We have also observed that the development of renal hypertrophy in the insulin-dependent diabetic BB rat and NOD mouse is associated with increased expression of TGF-β1 in the kidney and that short- term administration of antibodies capable of neutralizing the activity of TGF-β in the streptozotocin mouse model of diabetes results in attenuation of whole kidney and glomerular hypertrophy and overexpression of mRNAs encoding matrix components. Together, these findings are consistent with the hypothesis that the diabetic state stimulates TGF-β expression in the kidney and that in turn this growth factor may mediate, in an autocrine/paracrine manner, some of the principal early manifestations of diabetic renal disease. Demonstrating a causal link between upregulation of glomerular TGF-β and the subsequent development of diabetic glomerulosclerosis will require long-term interventional studies designed to intercept the TGF-β system in the kidney.",
author = "Kumar Sharma and Ziyadeh, {F. N.}",
year = "1995",
month = "1",
day = "1",
language = "English (US)",
volume = "44",
pages = "1139--1146",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "10",

}

TY - JOUR

T1 - Hyperglycemia and diabetic kidney disease

T2 - The case for transforming growth factor-β as a key mediator

AU - Sharma, Kumar

AU - Ziyadeh, F. N.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Renal cells are a rich source of transforming growth factor (TGF)-β, and they serve as targets for its actions. Our hypothesis that activation of the TGF-β system in the kidney is implicated in the development of diabetic renal disease stems from the close similarity of actions of TGF-β and high ambient glucose on renal cell growth and extracellular matrix metabolism. Proximal tubule cells and glomerular mesangial cells cultured in high glucose concentration express increased TGF-β1 mRNA and protein levels, and treatment with anti-TGF-β antibodies results in prevention of the effects of high glucose to induce cellular hypertrophy and stimulate collagen biosynthesis. Several in vive studies by different groups of investigators have reported overexpression of TGF-β in the glomeruli in human and experimental diabetes. We have also observed that the development of renal hypertrophy in the insulin-dependent diabetic BB rat and NOD mouse is associated with increased expression of TGF-β1 in the kidney and that short- term administration of antibodies capable of neutralizing the activity of TGF-β in the streptozotocin mouse model of diabetes results in attenuation of whole kidney and glomerular hypertrophy and overexpression of mRNAs encoding matrix components. Together, these findings are consistent with the hypothesis that the diabetic state stimulates TGF-β expression in the kidney and that in turn this growth factor may mediate, in an autocrine/paracrine manner, some of the principal early manifestations of diabetic renal disease. Demonstrating a causal link between upregulation of glomerular TGF-β and the subsequent development of diabetic glomerulosclerosis will require long-term interventional studies designed to intercept the TGF-β system in the kidney.

AB - Renal cells are a rich source of transforming growth factor (TGF)-β, and they serve as targets for its actions. Our hypothesis that activation of the TGF-β system in the kidney is implicated in the development of diabetic renal disease stems from the close similarity of actions of TGF-β and high ambient glucose on renal cell growth and extracellular matrix metabolism. Proximal tubule cells and glomerular mesangial cells cultured in high glucose concentration express increased TGF-β1 mRNA and protein levels, and treatment with anti-TGF-β antibodies results in prevention of the effects of high glucose to induce cellular hypertrophy and stimulate collagen biosynthesis. Several in vive studies by different groups of investigators have reported overexpression of TGF-β in the glomeruli in human and experimental diabetes. We have also observed that the development of renal hypertrophy in the insulin-dependent diabetic BB rat and NOD mouse is associated with increased expression of TGF-β1 in the kidney and that short- term administration of antibodies capable of neutralizing the activity of TGF-β in the streptozotocin mouse model of diabetes results in attenuation of whole kidney and glomerular hypertrophy and overexpression of mRNAs encoding matrix components. Together, these findings are consistent with the hypothesis that the diabetic state stimulates TGF-β expression in the kidney and that in turn this growth factor may mediate, in an autocrine/paracrine manner, some of the principal early manifestations of diabetic renal disease. Demonstrating a causal link between upregulation of glomerular TGF-β and the subsequent development of diabetic glomerulosclerosis will require long-term interventional studies designed to intercept the TGF-β system in the kidney.

UR - http://www.scopus.com/inward/record.url?scp=0029076281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029076281&partnerID=8YFLogxK

M3 - Review article

C2 - 7556948

AN - SCOPUS:0029076281

VL - 44

SP - 1139

EP - 1146

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

ER -