Expression of hypoxia inducible factor-1α during liver regeneration induced by partial hepatectomy in rats

Background/Aims: It has been well established that hypoxia inducible factor-1 alpha (HIF-1 alpha) transcribes essential factors in cell preservation, including angiogenesis, during hypoxia. However, the transition of HIF-1 alpha expression during liver regeneration remains unknown. In this study, a role of HIF-1 alpha was experimentally elucidated in relation to sinusoidal endothelial reconstruction during liver regeneration. Methods: Expression of HIF-1 alpha was evaluated in the regenerating liver following 70% hepatectomy in rats. Expressions of nuclear HIF-1 alpha, vascular endothelial growth factor (VEGF) and fms-like tyrosine kinase-1 (flt-1) were measured by Western blot and liver blood flow by a laser Doppler. Sinusoidal endothelial cell area (SECA) and HIF-1 alpha were localized by immunohistochemistry. HIF-1 alpha mRNA was measured by reverse transcription-polymerase chain reaction. Result: Liver blood flow and SECA were lowest 36 and 72 h following hepatectomy, respectively. Nuclear HIF-1 alpha peaked at 24 h and continuously increased 72 120 h following hepatectomy. This transition was fully supported by histological HIF-1 alpha expression and HIF-1 alpha mRNA up-regulation. VEGF and flt-1 peaked at 120 and 12 h, respectively. Conclusions: A significant evaluation in HIF-1 alpha expression was revealed in regenerating rat livers. HIF-1 alpha expression was preceded by VEGF and flt-1 expression and thus may be related to sinusoidal endothelial reconstruction.