肝细胞生长因子介导的 Dll4-Notch-Hey2 信号通路的激活作用。

Effects of hepatocyte growth factor-mediated activation of Dll4-Notch-Hey2 signaling pathway.

机构信息

Department of Laboratory Diagnosis, Central Hospital of Xianyang, Xianyang, Shaanxi 712000, China.

出版信息

Chin Med J (Engl). 2011 Jan;124(1):127-31.

Abstract

BACKGROUND

Hepatocyte growth factor (HGF) treats ischemic disease by promoting arteriogenesis, however, its mechanism of action is not known. The notch signaling pathway plays an important role in neovascularization. The relationship between the proliferation and migration ability of artery endothelial cells and the Dll4-Notch-Hey2 signaling pathway in the process of arteriogenesis was investigated as a mechanism of action of HGF.

METHODS

Based on the prophase study cells and supernatant were harvested at the indicated time after human femoral artery endothelial cells (HFAECs) were infected with adenovirus-HGF (Ad-HGF) at 200 pfu/cell. Cells were analyzed for HGF expression and Notch1, Dll4 and Hey2 expression by ELISA and reverse transcription-PCR (RT-PCR). The changes in the proliferation and migration ability of HFAECs were observed by MTT and Transwell migration experiments. Ad-GFP-infected HFAECs were used as control.

RESULTS

Compared with the control group the Ad-HGF group's HGF expression was not increased with time, and the induction by HGF of Notch1, Dll4 and Hey2 gene transcription was not enhanced with an increase of HGF. The proliferation ability of Ad-HGF-transduced HFAECs was enhanced and their migration ability was also enhanced in the presence of HGF.

CONCLUSIONS

Through activating the Dll4-Notch-Hey2 signaling pathway, HGF indirectly promotes the proliferation and migration ability of cells, so that offspring artery branches are formed.

摘要

背景

肝细胞生长因子（HGF）通过促进动脉生成来治疗缺血性疾病，但作用机制尚不清楚。Notch 信号通路在血管新生中发挥着重要作用。本研究旨在探讨 HGF 作用机制，即研究动脉内皮细胞增殖和迁移能力与 Dll4-Notch-Hey2 信号通路的关系。

方法

在感染腺病毒-HGF（Ad-HGF）200pfu/cell 后，于不同时间点收集人股动脉内皮细胞（HFAEC）的细胞和上清液，通过 ELISA 和逆转录-PCR（RT-PCR）分析 HGF 表达和 Notch1、Dll4 和 Hey2 表达。通过 MTT 和 Transwell 迁移实验观察 HFAEC 增殖和迁移能力的变化。用感染 Ad-GFP 的 HFAEC 作为对照。