Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production.

Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production. Research Abstract Details 

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Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production. Abstract Text:

Krag,Jens R Nyengaard,Lise Wogensen,

BACKGROUND: There is a correlation between renal graft rejection and blood glucose (BG) levels. Furthermore, diabetic patients may develop non-diabetic renal diseases, which in some circumstances progress rapidly. Since transforming growth factor-beta1 (TGF-beta) levels are elevated in many renal diseases, the accelerated progression may be due to interactions between glucose and locally produced TGF-beta1. Therefore, we investigated the effect of mild hyperglycaemia on glomerular morphology and collagen production in TGF-beta1 transgenic mice. METHODS: To achieve BG concentrations of approximately 15 mmol/l in TGF-beta1 transgenic and non-transgenic mice, we used multiple streptozotocin (STZ) injections, and after 8 weeks, we measured the changes in glomerular morphology and total collagen content. We also analysed extracellular matrix (ECM) and protease mRNA levels using real-time polymerase chain reaction (PCR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK) expression by immunohistochemistry. RESULTS: Mild hyperglycaemia alone had no effect on glomerular structure or ECM deposition. Over-expression of TGF-beta1 increased basement membrane thickness (BMT) and the mesangial volume fraction. Furthermore, it augmented ECM, Matrix metalloproteinase-2 (MMP), MMP-9, plasminogen activator inhibitor-1 (PAI) and tissue inhibitor of metalloproteinase-1 (TIMP) gene expression and pERK1/2 immunostaining. Elevated BG in combination with TGF-beta1 resulted in enlargement of glomerular volume, total mesangial volume and renal collagen content. Moreover, high BG exaggerated TGF-beta1-induced changes in the BMT, MMP-2 and TIMP-1 expression and pERK1/2 staining. CONCLUSION: Even moderate elevations in BG accelerate the progression of those kidney diseases in which TGF-beta1 is involved. This emphasizes the importance of strict BG control in renal transplant patients and diabetic patients with renal malfunctions unrelated to diabetes.

Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production. Publishing Authors By Initials

S Krag,JR Nyengaard,L Wogensen,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta: transforming growth factor beta1 research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta: transforming growth factor beta1 research

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Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nephrology, dialysis, transplantation : official p

VOLUME: 22

Page Numbers: 2485-96

Journal Abbreviation: Nephrol. Dial. Transplant.

ISSN: 0931-0509

DAY: 23

MONTH: 04

YEAR: 2007

Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production. Information

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LANGUAGE: eng

NlmUniqueID: 8706402

Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta1

MESH TERMS: metabolism

Chemical & Substance for Abstract: Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production. Information

Substance Name: Peptide Hydrolases

Registry Number: EC 3.4.-

Grant and Affiliation Information for Combined effects of moderately elevated blood glucose and locally produced TGF-beta1 on glomerular morphology and renal collagen production.

AFFILIATION: Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Aarhus C, Denmark. soeren.krag@ki.au.dk

Country: England

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MEDLINETA: Nephrol Dial Transplant

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