中国药理学通报2024，Vol.40Issue(9)：1658-1664,7.DOI:10.12360/CPB202405072
PGE2通过EP4/PKA信号通路调控滑膜细胞OAT1的表达及CP-25的作用
PGE2 regulates expression of OAT1 in synoviocytes via EP4/PKA signaling pathway and effect of CP-25
摘要
Abstract
Aim To investigate the regulatory mecha-nism of prostaglandin E2(PGE2)on the membrane expression of organic anion transporter 1(OAT1)in synoviocytes and the effect of paeoniflorin-6'-O-ben-zene sulfonate(CP-25).Methods Immunofluores-cence was used to detect the effects of CP-25 on the expression of OAT1 and prostaglandin E receptor 4(EP4)in PGE2 stimulated synoviocytes.EP4 agonists(TCS2510)and antagonists(GW627368X)were used to explore the role of EP4 in regulation of OAT1.CP-25 and protein kinase A(PKA)inhibitor H-89 were used to investigate the effects of CP-25 and PKA on OAT1 expression in synoviocytes.Results Membrane expression of EP4 and OAT1 was down-regulated with-in 0～10 min,and thereby up-regulated between 20～60 min in the presence of PGE2 simulation(P＜0.05).CP-25 significantly up-regulated the expres-sions of OAT1 and EP4 in PGE2 stimulated synovio-cytes(P＜0.05).TCS2510 significantly up-regulated the expression of OAT1 in cell membrane of synovio-cytes(P＜0.01).CP-25 up-regulated the expression of OAT1 in PGE2-treated cells,while the effect of CP-25 on expression of OAT1 was significantly inhibited after the together use of GW627368X and H-89.(P＜0.01).Conclusions PGE2-mediated EP4/PKA sig-naling pathway regulates the expression of OAT1 on membranes of synoviocytes.CP-25 can significantly in-crease the membrane expression of OAT1 in synovio-cytes by activating the EP4/PKA signaling pathway.关键词
芍药苷-6'-O-苯磺酸酯/滑膜细胞/有机阴离子转运蛋白1/前列腺素E2/前列腺素E受体4/蛋白激酶AKey words
paeoniflorin-6'-O-benzene sulfonate/sy-noviocyte/organic anion transporter 1/prostaglandin E2/EP4/PKA引用本文复制引用
肖康俊,高锦张,王勇,王斌,魏伟,王春..PGE2通过EP4/PKA信号通路调控滑膜细胞OAT1的表达及CP-25的作用[J].中国药理学通报,2024,40(9):1658-1664,7.基金项目
安徽省自然科学基金资助项目(No 2008085QH402) （No 2008085QH402）
