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Jens Randel Nyengaard

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

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  • Research Laboratory for Biochemical Pathology
  • Stereological Research Laboratory
  • Institute of Clinical Medicine
  • The Department of Pathology - ÅKH
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.
Udgivelsesdato: 2007-Sep
Original languageEnglish
JournalNephrology, Dialysis, Transplantation
Volume22
Issue9
Pages (from-to)2485-96
Number of pages11
ISSN0931-0509
DOIs
Publication statusPublished - 2007

    Research areas

  • Animals, Blood Glucose, Body Weight, Collagen, Extracellular Matrix, Extracellular Matrix Proteins, Extracellular Signal-Regulated MAP Kinases, Gene Expression Regulation, Glomerular Basement Membrane, Glomerular Mesangium, Immunohistochemistry, Kidney Glomerulus, Male, Mice, Mice, Inbred C57BL, Peptide Hydrolases, Phosphoproteins, Protease Inhibitors, Transforming Growth Factor beta, Transforming Growth Factor beta1

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