环孢素A可在体外通过MAPK/ERK1/2介导的NF-κB和Ca2+/钙调磷酸酶/NFAT信号转导促进人孕早期滋养层迁移

Cyclosporine A promotes in vitro migration of human first-trimester trophoblasts via MAPK/ERK1/2-mediated NF-κB and Ca2+/ calcineurin/NFAT signaling
作者:Wang, S.-C., Tang, Ch.-L., Piao, H.-L., Zhu, R., S
机构: 复旦大学上海医学院附属妇产科医院 生殖免疫学实验室
期刊: PLACENTA2013年4月4期34卷

Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, 413# Zhaozhou Road, Shanghai 200011, China

Introduction: As a calcineurin inhibitor in T-cell activation, cyclosporine A (CsA) has provided the pharmacologic foundation for organ transplantation. We have previously demonstrated that CsA promotes trophoblast growth and invasion in vitro. Here, we further investigated the regulation of CsA on trophoblast migration and the intracellular signaling pathways involved. Methods: We evaluated the migration of human primary trophoblasts by using transwell migration assay. CsA-mediated induction of nuclear factor-kappa B (NF-κB) was evaluated by cotransfection with luciferase reporter constructs and luciferase activity assays. Results: Treatment with CsA-promoted migration of primary trophoblasts and the HTR8 cell line in a dose-dependent manner. CsA also increased NF-κB-transcriptional activity in trophoblasts in time- and dose-dependent manners. Pharmacologically inhibiting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1/2 signaling with U0126 attenuated the CsA-induced cell migration and NF-κB activity in trophoblasts. Furthermore, pretreatment with PDTC, a specific NF-κB inhibitor, inhibited the CsA-induced migration of trophoblasts in dose-dependent manners. Although NFAT activation by ionomycin via calcineurin is accompanied by increased transactivation of NF-κB, pretreatment with the NFAT inhibitor did not affect NF-κB-transcriptional activity. Interestingly, ionomycin and CsA synergize to transactivate NF-κB. Ionomycin-inhibited basal migration of trophoblasts, and pretreatment with CsA reversed the ionomycin-inhibited trophoblast migration. However, the NFAT inhibitor increased basal migration, but not CsA-induced migration, of trophoblasts. Conclusion: These observations indicate that both the MAPK/ERK/NF-κB pathway and Ca2+/calcineurin/NFAT pathways are involved in the CsA-promoted trophoblast migration. Our findings may help expand the clinical applications of this drug in trophoblast disorder. © 2013 Elsevier Ltd. All rights reserved.
 

Li, D.-J.; Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, 413# Zhaozhou Road, Shanghai 200011, China; email:djli@shmu.edu.cn

通讯作者:Li, D.-J.; Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, 413# Zhaozhou Road, Shanghai 200011, China; email:djli@shmu.edu.cn
学科代码:妇产科学   关键词:Ring_A_spore_element_can_be_me
来源: Scopus
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