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Expression of hypoxia inducible factor‐1α during liver regeneration induced by partial hepatectomy in rats
Author(s) -
Maeno Hiroshi,
Ono Takashi,
Dhar Dipok Kumar,
Sato Takashi,
Yamanoi Akira,
Nagasue Naofumi
Publication year - 2005
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2005.01144.x
Subject(s) - liver regeneration , angiogenesis , hypoxia inducible factors , hepatectomy , hypoxia (environmental) , vascular endothelial growth factor , western blot , biology , immunohistochemistry , tyrosine aminotransferase , medicine , endocrinology , regeneration (biology) , chemistry , immunology , cancer research , microbiology and biotechnology , vegf receptors , biochemistry , gene , enzyme , surgery , resection , oxygen , enzyme inducer , organic chemistry
Background/Aims: It has been well established that hypoxia inducible factor‐1α (HIF‐1α) transcribes essential factors in cell preservation, including angiogenesis, during hypoxia. However, the transition of HIF‐1α expression during liver regeneration remains unknown. In this study, a role of HIF‐1α was experimentally elucidated in relation to sinusoidal endothelial reconstruction during liver regeneration. Methods: Expression of HIF‐1α was evaluated in the regenerating liver following 70% hepatectomy in rats. Expressions of nuclear HIF‐1α, 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‐1α were localized by immunohistochemistry. HIF‐1α 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‐1α peaked at 24 h and continuously increased 72–120 h following hepatectomy. This transition was fully supported by histological HIF‐1α expression and HIF‐1α mRNA up‐regulation. VEGF and flt‐1 peaked at 120 and 12 h, respectively. Conclusions: A significant evaluation in HIF‐1α expression was revealed in regenerating rat livers. HIF‐1α expression was preceded by VEGF and flt‐1 expression and thus may be related to sinusoidal endothelial reconstruction.