{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T15:14:32Z","timestamp":1772896472719,"version":"3.50.1"},"reference-count":45,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2003,5,1]]},"abstract":"<jats:p>Vanadium pentoxide (V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>) 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<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) 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<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>treatment. V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>-induced HB-EGF mRNA expression was abolished by N-acetyl-l-cysteine, suggesting an oxidant-mediated effect. Exogenous H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>(&gt;10 \u03bcM) mimicked the effect of V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>in upregulating HB-EGF expression. Fibroblasts spontaneously released low levels of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>(1\u20132 \u03bcM), and the addition of V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>depleted the endogenous H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>pool within minutes. V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>caused a subsequent increase of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>into the culture medium at 12 h. However, the burst of V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>-induced H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>occurred after V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>-induced HB-EGF mRNA expression at 3 h, indicating that the V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>-stimulated H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>burst did not mediate HB-EGF expression. Either V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>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<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>- or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-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<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>in V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>treated cells, yet the action of V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>in upregulating HB-EGF is oxidant dependent and could be due to the reaction of V<jats:sub>2<\/jats:sub>O<jats:sub>5<\/jats:sub>with endogenous H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>.<\/jats:p>","DOI":"10.1152\/ajplung.00189.2002","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:21:34Z","timestamp":1425414094000},"page":"L774-L782","source":"Crossref","is-referenced-by-count":33,"title":["Vanadium-induced HB-EGF expression in human lung fibroblasts is oxidant dependent and requires MAP kinases"],"prefix":"10.1152","volume":"284","author":[{"given":"Jennifer L.","family":"Ingram","sequence":"first","affiliation":[{"name":"Laboratories of Pulmonary Pathobiology and"}]},{"given":"Annette 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