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.

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