PGE2 regulates expression of OAT1 in synoviocytes via EP4/PKA signaling pathway and effect of CP-25
- VernacularTitle: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
- Author:
Kang-Jun XIAO
1
;
Jin-Zhang GAO
;
Yong WANG
;
Bin WANG
;
Wei WEI
;
Chun WANG
Author Information
- Keywords: paeoniflorin-6'-O-benzene sulfonate; sy-noviocyte; organic anion transporter 1; prostaglandin E2; EP4; PKA
- From: Chinese Pharmacological Bulletin 2024;40(9):1658-1664
- CountryChina
- Language:Chinese
- 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.
