Resistin impairs activation of protein C by suppressing EPCR and increasing SP1 expression

• Published in: Biomedicine & pharmacotherapy Vol. 109; pp. 930 - 937
• Main Authors: Zhang, Pei, Liu, Yu, Su, Jiangli, Bai, Jie, Zhao, Shikai, Zhao, Shouguo
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2019; Elsevier
• Subjects: Activated protein C; Dose-Response Relationship, Drug; Endothelial Protein C Receptor - antagonists & inhibitors; Endothelial Protein C Receptor - biosynthesis; EPCR; Gene Expression; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; HUVEC; Protein C - metabolism; Resistin; Resistin - pharmacology; SP1; Sp1 Transcription Factor - biosynthesis; Sp1 Transcription Factor - genetics; HUVEC; EPCR; Activated protein C; SP1; Resistin
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.09.160

•Resistin inhibits thrombin induced protein C activation.•Resistin reduces the expression of EPCR but not TM in HUVECs, mediated by SP1.•Blockage of SP1 abolished the effects of Resistin on protein C activation. 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.