Expression of Notch-Hif-1α signaling pathway in liver regeneration of rats
- J Int Med Res. 2020 Sep;48(9):300060520943790. doi: 10.1177/0300060520943790.
- 1. Department of Blood Transfusion, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
- 2. Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
- 3. Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
- 4. Department of General Surgery, Zengcheng People's Hospital, Zengcheng, China.
- 5. Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
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.