Vanadium-induced HB-EGF expression in human lung fibroblasts is oxidant dependent and requires MAP kinases

Journal Article (Journal Article)

Vanadium pentoxide (V O ) is a transition metal derived from the burning of petrochemicals that causes airway fibrosis and remodeling. Vanadium compounds activate many intracellular signaling pathways via the generation of hydrogen peroxide (H O ) or other reactive oxygen species. In this study, we investigated the regulation of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in human lung fibroblasts after V O treatment. V O -induced HB-EGF mRNA expression was abolished by N-acetyl-L-cysteine, suggesting an oxidant-mediated effect. Exogenous H O (>10 μM) mimicked the effect of V O in upregulating HB-EGF expression. Fibroblasts spontaneously released low levels of H O (1-2 μM), and the addition of V O depleted the endogenous H O pool within minutes. V O caused a subsequent increase of H O into the culture medium at 12 h. However, the burst of V O -induced H O occurred after V O -induced HB-EGF mRNA expression at 3 h, indicating that the V O -stimulated H O burst did not mediate HB-EGF expression. Either V O or H O activated ERK-1/2 and p38 MAP kinase. Inhibitors of the ERK-1/2 pathway (PD-98059) or p38 MAP kinase (SB-203580) significantly reduced either V O or H O -induced HB-EGF expression. These data indicate that vanadium upregulates HB-EGF via ERK and p38 MAP kinases. The induction of HB-EGF is not related to a burst of H O in V O treated cells, yet the action of V O in upregulating HB-EGF is oxidant dependent and could be due to the reaction of V O with endogenous H O . 2 5 2 2 2 5 2 5 2 2 2 5 2 2 2 5 2 2 2 5 2 2 2 5 2 2 2 5 2 5 2 2 2 5 2 2 2 5- 2 2 2 2 2 5 2 5 2 5 2 2

Full Text

Duke Authors

Cited Authors

  • Ingram, JL; Rice, AB; Santos, J; Van Houten, B; Bonner, JC

Published Date

  • May 1, 2003

Published In

Volume / Issue

  • 284 / 5 28-5

International Standard Serial Number (ISSN)

  • 1040-0605

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00189.2002

Citation Source

  • Scopus