Department of Blood Transfusion, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
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.
J Int Med Res. 2020 Sep;48(9):300060520943790. doi: 10.1177/0300060520943790.
To investigate whether the Notch-Hif-1α signaling pathway is involved in liver regeneration.
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 (), hairy and enhancer of split-1 (), and vascular endothelial growth factor (), and the protein expression of NICD and HIF-1α, respectively.
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 and mRNA levels and NICD and HIF-1α protein expression levels were all down-regulated by Fli-06 treatment.
Notch-Hif-α signaling pathway activation plays an important role in liver regeneration, where it may contribute toward liver cell proliferation.
探讨 Notch-Hif-1α 信号通路是否参与肝脏再生。
将大鼠分为两组，每天腹腔注射生理盐水（对照组）或 γ-分泌酶抑制剂 Fli-06，连续 2 天。切除大鼠肝脏的 2/3，在切除后特定时间点处死大鼠，以分析剩余肝脏。计算每组的肝/体重比，并通过免疫染色和 Western blot 检测细胞增殖标志物 PCNA 和 Ki-67 的表达。通过实时 PCR 和 Western blot 比较 Notch 同源物-1()、毛状和分裂增强子 1() 和血管内皮生长因子() 的 mRNA 表达，以及 NICD 和 HIF-1α 的蛋白表达。
实验组的肝/体重比和 Ki-67 和 PCNA 阳性细胞数量明显低于对照组，表明 Notch 信号通路被 Fli-06 阻断后肝脏再生水平降低。Fli-06 处理后，和 mRNA 水平以及 NICD 和 HIF-1α 蛋白表达水平均下调。
Notch-Hif-α 信号通路的激活在肝脏再生中发挥重要作用，可能有助于肝实质细胞增殖。
