EdCC reduces myocardial ischemia-reperfusion injury via MEK-ERK signaling pathway / 中国病理生理杂志

ABSTRACT

AIM:To investigate the myocardial protective effect of endometrial stem cell ( EnSC)-derived cyto-kine cocktail ( EdCC) on myocardial ischemic reperfusion injury and the MEK-ERK signaling pathway.METHODS: A mouse model of myocardial ischemic reperfusion injury was established.Infarct area, cell apoptosis, and expression of cleaved caspase-3 and phosphorylatied ERK1/2 were determined by TTC/Evans blue staining, TUNEL assay and Western blot, respectively.RESULTS:The mesenchymal characteristics were observed in the EnSCs with expressing CD90 and in absence of CD34 and CD45.EdCC contained (6 811 ±312) ng/g epidermal growth factor (EGF) protein.The phospho-rylation of ERK1/2 markedly increased after injection of EdCC, but was abolished by MEK1 inhibitor PD98059 ( 5 mg/kg) .EdCC decreased the infarct area and apoptotic cell number in the border zone and inhibited caspase-3 activation. However, the effects were abolished by MEK1 specific inhibitor PD98059.EGF did not decrease the infarct area, but the EGF receptor antagonist AG-1487 (6 mg/kg) partly abolished the myocardial protective effect of EdCC.CONCLUSION:EdCC protects the myocardium from ischemic reperfusion injury via activating MEK1-ERK signaling pathway, indicating an essential role in the transmission of stem cell therapy from the cell transplantation to cytokine based strategy.