Expression of Notch–Hif-1α signaling pathway in liver regeneration of rats. Issue 9 (September 2020)

• Record Type: Journal Article
• Authors: Li, Yanshan; Xu, Yunxiuxiu; Wang, Ruomei; Li, Wenxin; He, Wenguang; Luo, Xinxi; Ye, Yibiao
• Is Part Of: Journal of international medical research. Volume 48:Issue 9(2020)
• Publication Date: 2020-09
• Subjects: Liver regeneration -- gamma-secretase inhibitors -- Notch intracellular domain -- Hif-1α -- Notch homolog-1 -- vascular endothelial growth factor -- hepatectomy; Medicine -- Periodicals; Pharmacology -- Periodicals; 610.5
• DOI: 10.1177/0300060520943790
• Languages: English
• ISSNs: 0300-0605

Abstract

Objective: To investigate whether the Notch–Hif-1α signaling pathway is involved in liver regeneration. Methods: Rats were divided into two groups and treated with daily intraperitoneal injections of saline (control) or the gamma-secretase inhibitor, Fli-06, for 2 days. Two-thirds of the rat livers were resected and rats were later euthanized at specific time points post-resection to analyze the remnant livers. Each group's liver/body weight ratio was calculated, and immunostaining and western blotting were used to determine the cell proliferation marker, PCNA and Ki-67 expression. Real-time PCR and western blotting were used to compare the mRNA expression of Notch homolog-1 ( Notch1 ), hairy and enhancer of split-1 ( Hes1 ), and vascular endothelial growth factor ( Vegf ), and the protein expression of NICD and HIF-1α, respectively. Results: The liver/body weight ratios and number of Ki-67- and PCNA-positive cells were significantly lower in the experimental group than the control group, indicating lower levels of liver regeneration following the disruption of Notch signaling by Fli-06. The Hes1 and Vegf mRNA levels and NICD and HIF-1α protein expression levels were all down-regulated by Fli-06 treatment. Conclusion: Notch–Hif-α signaling pathway activation plays an important role in liver regeneration, where it may contribute toward liver cell proliferation.