Chloroform induces HIF-1 alpha-dependent VEGF expression in human keratinocytes

Abstract

Vascular endothelial growth factor (VEGF), a primary angiogenic factor, can be expressed under various pathological conditions. We showed that VEGF was upregulated when human keratinocytes were treated with the volatile organic compound chloroform. We investigated the regulation of VEGF expression by the transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha). HIF-1 alpha, a protein that normally mediates the expression of proteins in hypoxia, controlled VEGF expression in human keratinocytes treated with chloroform. No significant change was seen in HIF-1 alpha mRNA level, consistent with previous reports that HIF-1 alpha protein is constitutively expressed and degraded. Furthermore, transfection of cells with plasmids that overexpressed HIF-1 alpha upregulated VEGF expression. Small interfering RNA against HIF-1 alpha suppressed chloroform-induced VEGF expression in keratinocytes, indicating that HIF-1 alpha was involved in VEGF expression. Thus, the results of this study indicated that HIF-1 alpha mediated the expression of VEGF in human keratinocytes treated with chloroform.