Overexpression of transforming growth factor-β1 mRNA is associated with up-regulation of glomerular tenascin and laminin gene expression in nonobese diabetic mice

C. W. Yang, M. Hattori, H. Vlassara, C. J. He, M. A. Carome, E. Yamato, S. Elliot, G. E. Striker, L. J. Striker

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Nonobese diabetic (NOD) mice spontaneously develop immune-mediated insulin-dependent diabetes mellitus and nephropathy, providing an opportunity to study the early molecular events in a model of diabetic glomerulosclerosis. The expression of several genes coding for growth factors and extracellular matrix was examined in microdissected glomeruli, by the use of reverse transcription-competitive polymerase chain reaction, in diabetic NOD mice (mean duration of diabetes, 28.5 ± 7 days) and age-matched nondiabetic NOD mice with normal glucose tolerance. The levels of mRNA coding tor transforming growth factor-β1, tenascin, and laminin B1 increased 1.9-, 2.0-, and 1.7-fold, respectively, whereas platelet-derived growth factor (PDGF)-B, α1 (IV) collagen, 72-kd collagenase, α-smooth muscle actin, and β-actin mRNA remained stable in the diabetic mice. The kidney advanced glycosylation endproducts levels increased 2.1 -fold in the diabetic mice, and the diabetic glomeruli showed an accumulation of tenascin and laminin but not of type IV collagen by immunofluorescence microscopy. There was no increase in cell number per glomerulus after the onset of diabetes, a finding consistent with stable PDGF-B and α-smooth muscle actin mRNA levels. These findings provide evidence that increased glomerular transforming growth factor-β1, but not PDGF-B, mRNA is associated with the up-regulation of tenascin and laminin expression after advanced glycosylation endproduct accumulation, early after the onset of diabetes.

Original languageEnglish (US)
Pages (from-to)1610-1617
Number of pages8
JournalJournal of the American Society of Nephrology
Volume5
Issue number8
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • advanced glycosylation endproducts
  • competitive polymerase chain reaction
  • extracellular matrix
  • glomerulosclerosis
  • growth factor

ASJC Scopus subject areas

  • Nephrology

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