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

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-1α (HIF-1α). HIF-1α, 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-1α mRNA level, consistent with previous reports that HIF-1α protein is constitutively expressed and degraded. Furthermore, transfection of cells with plasmids that overexpressed HIF-1α upregulated VEGF expression. Small interfering RNA against HIF-1α suppressed chloroform-induced VEGF expression in keratinocytes, indicating that HIF-1α was involved in VEGF expression. Thus, the results of this study indicated that HIF-1α mediated the expression of VEGF in human keratinocytes treated with chloroform.