Expression of hypoxia inducible factor-1α and its correlation with phosphoenolpyruvate carboxykinase after portal vein ligation in rats

• DOI: 10.1016/j.lfs.2017.09.010
• Publication Date: 2017-09-28T04:46:51Z
• Authors: Changjun Jia; Hua Yang; Chaoliu Dai; Feng Xu; Songlin Peng; Yang Zhao; Chuang Zhao; Liang Zhao
• Keywords: Male; 0301 basic medicine; Time Factors; Portal Vein; Blotting, Western; Gluconeogenesis; Intracellular Signaling Peptides and Proteins; Enzyme-Linked Immunosorbent Assay; Hypoxia-Inducible Factor 1, alpha Subunit; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Liver; Animals; Regeneration; Phosphoenolpyruvate Carboxykinase (GTP); Ligation

Portal vein ligation (PVL) has been used to effectively increase future liver remnant (FLR) in hepatectomy for treatment of liver cancer. However, the underlying molecular mechanisms have not been well characterized. The present study aimed to determine expression of hypoxia inducible factor-1alpha (HIF-1α) in response to PVL and assess the correlation of HIF-1α and phosphoenolpyruvate carboxykinase (PEPCK).Male Sprague-Dawley rats underwent PVL and were sacrificed at different time points (12, 24, 48, 72, and 168h) after surgery. Hepatic HIF-1α expression in the regenerating liver was assessed by Western blot and immunohistochemistry, in parallel; PEPCK levels were quantified by ELISA.We found that the ligated liver lobes diminished progressively, whereas the unligated lobes underwent compensatory regeneration after 70% ligation of portal vein branches in the PVL group. Hepatic HIF-1α and PEPCK levels in the unligated liver lobes were significantly increased in the PVL group compared to the hepatic artery ligation (HAL) and the sham (SH) operation groups. Pearson's correlation analysis revealed positive correlation between HIF-1α expression and PEPCK levels in the unligated lobes after PVL. Further analysis indicated that higher levels of HIF-1α and PEPCK in response to liver regeneration were paralleled by an increase in the ratio of the mass and volume of unligated lobes to the whole liver.HIF-1α was up-regulated and positively correlated with PEPCK during liver regeneration after PVL in rats, suggesting that HIF-1α may modulate hepatic gluconeogenesis through PEPCK, which may ensure the energy supply required for liver regeneration.