Abstract:

Objective To investigate the effect and mechanism of activated platelet⁃induced angiogenesis on EMT of IMECs. Methods The effect of activated platelets on the angiogenesis of IMECs was investigated by comparing the changes in cell migration capacity and lumen formation of IMECs with and without PI3K/mTOR inhibitor BEZ235.To observe the effects on the protein expression of phosphorylation⁃related proteins and HIF⁃1α in the PI3K/AKT/mTOR signaling pathway，and the effects on the expression changes of fibrosis⁃related factors E⁃cadherin，α ⁃SMA，and CollagenI and gene expression levels. Results The IMECs′s proportion obtained by culture and identified as endothelial cells by morphological features of inverted microscope was over 95% . After adding ADP to resting platelets ，the concentration of p ⁃selectin antibody detected by FCM was significantly increased（P < 0.01），indicating that the number of activated platelets was significantly increased. Compared with the addition of PI3K/mTOR inhibitor BEZ235，activated platelet stimulation enhanced the cell migration ability and lumen formation ability of IMECs，and inhibited PI3K，AKT，mTOR phosphorylated protein and HIF⁃1α protein，the protein production and gene expression of fibrosis ⁃ related factors α⁃SMA and CollagenI were signifi⁃ cantly suppressed，while E⁃cadherin protein production and gene expression were up⁃regulated. Conclusion The mechanism of activating platelet⁃induced EMTs in IMECs cells may be achieved by promoting angiogenesis through the PI3K/AKT signaling pathway.

Key words:

intestinal microvascular endothelial cells, platelet activation, angiogenesis, EMT, PI3K/AKT/mTOR