The effect of lipopolysaccharide (LPS) on the anti-coagulant factor endothelial protein C receptor (EPCR) in vivo

摘要

Background: The endothelial protein C receptor (EPCR) is the main member in anticoagulant system. EPCR is regulated by various molecules in its upstream. But most of studies about EPCR and its regulation mechanism are derived from in-vitro experiments. Aims: To observe the effect of Lipopolysaccharide (LPS) on EPCR and the potential regulatory molecules in vivo. Methods: We treated mice with LPS solution and collected the total protein of thoracic aorta, heart and lung tissues to determine the expressions of EPCR, tumor necrosis factor-α converting enzyme (ADAM17), p-ERK and protein kinase C δ (PKC δ) by immunoblotting. Results: The results showed that, in normal mice, thoracic aorta only expressed truncated EPCR, but heart and lung expressed truncated EPCR and mature EPCR. LPS treatment caused the reduction of both of the two EPCR. Further results exhibited that LPS treatment increased the expressions of ADAM17, p-ERK and PKC δ protein in the three tissues. Conclusion: LPS may activate PKC δ and ERK pathway to regulate the decrease or shedding of EPCR mediated by ADAM17 in vivo. These findings may help to elucidate the mechanism of coagulation disorders caused by invading pathogens in addition to therapeutic targets.