Xu Chen, You Xingji, Liu Weina, Sun Qianqian, Ding Xiaoying, Huang Ying, Ni Xin
Department of PhysiologySecond Military Medical University, 800 Xiangyin Road, Shanghai 200433, ChinaDepartment of Obstetrics and GynecologyChanghai Hospital, Shanghai, ChinaMaternity and Child Health Hospital of Pudong New District599 Hongfeng Road, Shanghai 201206, China.
Department of PhysiologySecond Military Medical University, 800 Xiangyin Road, Shanghai 200433, ChinaDepartment of Obstetrics and GynecologyChanghai Hospital, Shanghai, ChinaMaternity and Child Health Hospital of Pudong New District599 Hongfeng Road, Shanghai 201206, China Department of PhysiologySecond Military Medical University, 800 Xiangyin Road, Shanghai 200433, ChinaDepartment of Obstetrics and GynecologyChanghai Hospital, Shanghai, ChinaMaternity and Child Health Hospital of Pudong New District599 Hongfeng Road, Shanghai 201206, China.
Reproduction. 2015 Jan;149(1):139-46. doi: 10.1530/REP-14-0479. Epub 2014 Oct 23.
Prostaglandin F2α (PGF2A) has multiple roles in the birth process in addition to its vital contractile role. Our previous study has demonstrated that PGF2A can modulate uterine activation proteins (UAPs) in cultured pregnant human myometrial smooth muscle cells (HMSMCs). The objective of this study was to define the signalling pathways responsible for PGF2A modulation of UAPs in myometrium. It was found that PGF2A stimulated the expression of (GJA1) connexin 43 (CX43), prostaglandin endoperoxide synthase 2 (PTGS2) and oxytocin receptor (OTR) in cultured HMSMCs. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked PGF2A-stimulated expression of CX43. The inhibitors of ERK, P38 and NFκB also blocked the effect of PGF2A on CX43 expression, whereas PI3K and calcineurin/nuclear factor of activated T-cells (NFAT) pathway inhibitors did not reverse the effect of PGF2A on CX43. For PTGS2 and OTR, PLC, PI3K, P38 and calcineurin/NFAT signalling pathways were involved in PGF2A action, whereas PKC and NFκB signalling were not involved. In addition, PGF2A activated NFAT, PI3K, NFκB, ERK and P38 signalling pathways. Our data suggest that PGF2A stimulates CX43, PTGS2 and OTR through divergent signalling pathways.
前列腺素F2α（PGF2A）在分娩过程中除了具有重要的收缩作用外，还具有多种功能。我们之前的研究表明，PGF2A可以调节培养的人妊娠子宫肌层平滑肌细胞（HMSMCs）中的子宫激活蛋白（UAPs）。本研究的目的是确定子宫肌层中PGF2A调节UAPs的信号通路。研究发现，PGF2A刺激培养的HMSMCs中连接蛋白43（CX43）、前列腺素内过氧化物合酶2（PTGS2）和催产素受体（OTR）的表达。磷脂酶C（PLC）和蛋白激酶C（PKC）的抑制剂可阻断PGF2A刺激的CX43表达。ERK、P38和NFκB的抑制剂也可阻断PGF2A对CX43表达的影响，而PI3K和钙调神经磷酸酶/活化T细胞核因子（NFAT）信号通路抑制剂并不能逆转PGF2A对CX43的作用。对于PTGS2和OTR，PLC、PI3K、P38和钙调神经磷酸酶/NFAT信号通路参与了PGF2A的作用，而PKC和NFκB信号通路未参与。此外，PGF2A激活了NFAT、PI3K、NFκB、ERK和P38信号通路。我们的数据表明，PGF2A通过不同的信号通路刺激CX43、PTGS2和OTR。
