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. 2005 Oct;25(5):1002-9.
doi: 10.1111/j.1478-3231.2005.01144.x.

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

Hiroshi Maeno  1 , Takashi Ono, Dipok Kumar Dhar, Takashi Sato, Akira Yamanoi, Naofumi Nagasue
Affiliations

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

Hiroshi Maeno et al. Liver Int. 2005 Oct.

Abstract

Background/aims: It has been well established that hypoxia inducible factor-1alpha (HIF-1alpha) transcribes essential factors in cell preservation, including angiogenesis, during hypoxia. However, the transition of HIF-1alpha expression during liver regeneration remains unknown. In this study, a role of HIF-1alpha was experimentally elucidated in relation to sinusoidal endothelial reconstruction during liver regeneration.

Methods: Expression of HIF-1alpha was evaluated in the regenerating liver following 70% hepatectomy in rats. Expressions of nuclear HIF-1alpha, 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-1alpha were localized by immunohistochemistry. HIF-1alpha 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-1alpha peaked at 24 h and continuously increased 72-120 h following hepatectomy. This transition was fully supported by histological HIF-1alpha expression and HIF-1alpha mRNA up-regulation. VEGF and flt-1 peaked at 120 and 12 h, respectively.

Conclusions: A significant evaluation in HIF-1alpha expression was revealed in regenerating rat livers. HIF-1alpha expression was preceded by VEGF and flt-1 expression and thus may be related to sinusoidal endothelial reconstruction.

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