Activation of Mesangial Cells by the Phosphatase Inhibitor Vanadate: Potential Implications for Diabetic Nephropathy

Ulrich O. Wenzel, Bruno Fouqueray, Purba Biswas, Giuseppe Grandaliano, Goutam Ghosh Choudhury, Hanna E. Abboud

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The metalion vanadate has insulin-like effects and has been advocated for use in humans as a therapeutic modality for diabetes mellitus. However, since vanadate is a tyrosine phosphatase inhibitor, it may result in undesirable activation of target cells. We studied the effect of vanadate on human mesangial cells, an important target in diabetic nephropathy. Vanadate stimulated DNA synthesis and PDGF B chain gene expression. Vanadate also inhibited total tyrosine phosphatase activity and stimulated tyrosine phosphorylation of a set of cellular proteins. Two chemically and mechanistically dissimilar tyrosine kinase inhibitors, genistein and herbimycin A, blocked DNA synthesis induced by vanadate. Vanadate also stimulated phospholipase C and protein kinase C. Downregulation of protein kinase C abolished vanadate-induced DNA synthesis. Thus, vanadate-induced mitogenesis is dependent on tyrosine kinases and protein kinase C activation. The most likely mechanism for the effect of vanadate on these diverse processes involves the inhibition of cellular phosphotyrosine phosphatases. These studies demonstrating that vanadate activates mesangial cells may have major implications for the therapeutic potential of vanadate administration in diabetes. Although vanadate exerts beneficial insulin-like effects and potentiates the effect of insulin in sensitive tissue, it may result in undesirable activation of other target cells, such as mesangial cells.

Original languageEnglish (US)
Pages (from-to)1244-1252
Number of pages9
JournalJournal of Clinical Investigation
Volume95
Issue number3
DOIs
StatePublished - Mar 1995

Keywords

  • Human kidney
  • Phospholipase C
  • Platelet-derived growth factor
  • Protein kinase C
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Activation of Mesangial Cells by the Phosphatase Inhibitor Vanadate: Potential Implications for Diabetic Nephropathy'. Together they form a unique fingerprint.

  • Cite this