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

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 HGE 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, DII4 and Hey2 expression by ELISA and reverse transcription-PCR （RT-PCR）. The changes in the proliferation and migration ability of HFAECs were observed by M-I-I- 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, DII4 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 DII4-Notch-Hey2 signaling pathway, HGF indirectly promotes the proliferation and migration ability of cells, so that offspring artery branches are formed.

Metabolic Pathway of Monounsaturated Lipids Revealed by In-Depth Structural Lipidomics by Mass Spectrometry

The study of lipid metabolism relies on the characterization of the lipidome,which is quite complex due to the structure variations of the lipid species.New analytical tools have been developed recently for characterizing fine structures of lipids,with C=C location identification as one of the major improvements.In this study,we studied the lipid metabolism reprograming by analyzing glycerol phospholipid compositions in breast cancer cell lines with structural specification extended to the C=C location level.Inhibition of the lipid desaturase,stearoyl-CoA desaturase 1,increased the proportion of n-10 isomers that are produced via an alternative fatty acid desaturase 2 pathway.However,there were different variations of the ratio of n-9/n-7 isomers in C18:1-containing glycerol phospholipids after stearoyl-CoA desaturase 1 inhibition,showing increased tendency in MCF-7 cells,MDA-MB-468 cells,and BT-474 cells,but decreased tendency in MDA-MB-231 cells.No consistent change of the ratio of n-9/n-7 isomers was observed in SK-BR-3 cells.This type of heterogeneity in reprogrammed lipid metabolism can be rationalized by considering both lipid desaturation and fatty acid oxidation,highlighting the critical roles of comprehensive lipid analysis in both fundamental and biomedical applications.