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Resistin impairs activation of protein C by suppressing EPCR and increasing SP1 expression
Pei Zhang1, Yu Liu1, Jiangli Su2
1Department of Endocrinology, Liaocheng People's Hospital, Liaocheng 252000, China.
Endothelial cells are vital to blood coagulation and maintain whole body hemostasis. Binding of endothelial cells to endothelial protein C receptor (EPCR) and thrombomodulin (TM) is essential to the formation of activated protein C (APC), one of the key factors regulating blood coagulation. In our study, we showed that resistin, an adipocyte hormone, suppresses thrombin-induced protein C activation in endothelial cells. Resistin treatment results in a reduction in EPCR expression, but not TM. Mechanistically, we demonstrate that resistin induces expression of the nuclear transcription factor SP-1, which could lead to downregulation of EPCR. Both inhibition and silencing of SP1 protein abolishes abnormal APC generation induced by resistin. Collectively, our data support a new role of resistin in disturbing APC formation.
Endothelial cells are vital to blood coagulation and maintain whole body hemostasis. Binding of endothelial cells to endothelial protein C receptor (EPCR) and thrombomodulin (TM) is essential to the formation of activated protein C (APC), one of the key factors regulating blood coagulation. In our study, we showed that resistin, an adipocyte hormone, suppresses thrombin-induced protein C activation in endothelial cells. Resistin treatment results in a reduction in EPCR expression, but not TM. Mechanistically, we demonstrate that resistin induces expression of the nuclear transcription factor SP-1, which could lead to downregulation of EPCR. Both inhibition and silencing of SP1 protein abolishes abnormal APC generation induced by resistin. Collectively, our data support a new role of resistin in disturbing APC formation.
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