Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-β

Fuad N. Ziyadeh, Kumar Sharma, Mark Ericksen, Gunter Wolf

Research output: Contribution to journalArticlepeer-review

544 Scopus citations

Abstract

Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of TGF-β. We tested whether the stimulation of extracellular matrix production is mediated by autocrine activation of TGF- β, a known prosclerotic cytokine. Addition of neutralizing anti-TGF-β antibody, but not normal rabbit IgG, significantly reduced the high glucose- stimulated incorporation of 3[H]proline. Denaturing SDS-PAGE revealed that mainly collagen types I and IV were stimulated by high (450 mg/dl) D-glucose. This high glucose-mediated increase in collagen synthesis was reduced by the anti-TGF-β antibody. Treatment of mesangial cells grown in normal (100 mg/dl) D-glucose with 2 ng/ml recombinant TGF-β1 mimicked the effects of high glucose. Furthermore, the anti-TGF-β antibody significantly reduced the increase in mRNA levels encoding α2(I) and α1(IV) collagens induced by high glucose. Thus, the high glucose-stimulated increase of collagen production in mesangial cells is mediated, at least in part, by autocrine TGF-β activation. We postulate that the interception of the glomerular activity of TGF-β may be an effective intervention in the management of diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)536-542
Number of pages7
JournalJournal of Clinical Investigation
Volume93
Issue number2
DOIs
StatePublished - Feb 1994

Keywords

  • collagen type I
  • collagen type IV
  • diabetic glomerulopathy
  • extracellular matrix
  • mouse kidney

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-β'. Together they form a unique fingerprint.

Cite this