title: Prostaglandin F2α regulates the expression of uterine activation proteins via multiple signalling pathways.
abstract: 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.
authors.affiliation: 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.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Xingji
authors.initials: X
authors.lastname: You
authors.affiliation: 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.
authors.forename: Weina
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ding
authors.affiliation: 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 nixin@smmu.edu.cn stassi22@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 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 nixin@smmu.edu.cn stassi22@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
mesh_terms: D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010120:Oxytocics / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D018045:Receptors, Oxytocin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; C569600:OXTR protein, human; D010120:Oxytocics; D018045:Receptors, Oxytocin; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human