Hepatology : official journal of the American Association for the Study of Liver Diseases
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The tissue repair response to hypoxic stimuli during wound healing includes enhanced production of angiogenic factors, such as vascular endothelial growth factor (VEGF). Hepatic stellate cells are oxygen-sensing cells, capable of producing VEGF. We hypothesized that hypoxia-stimulated signaling in activated stellate cells mediate VEGF secretion during liver injury. ⋯ Hypoxic induction of VEGF was also demonstrated in primary stellate cell cultures and after in vivo injury. Hypoxia stimulates cell signaling in stellate cells, culminating in the rapid induction of VEGF and Flt-1 mRNA expression and VEGF secretion. The hypoxic induction of VEGF is mimicked by NO and may be of mechanistic importance in the pathogenesis of hepatic wound healing and hepatocarcinogenesis.