Leukemia inhibitory factor induces corticotropin-releasing hormone in mouse trophoblast stem cells
Leukemia inhibitory factor induces corticotropin-releasing hormone in mouse trophoblast stem cells
复制标题
DOI：
10.1016/j.bbrc.2019.11.059
复制
发表时间：
2020-01-29
影响因子：
3.1
通讯作者：
Hatta, Toshihisa
中科院分区：
文献类型：
--
作者：
Wang, He;Tsukada, Tsuyoshi;Hatta, Toshihisa
已有研究表明，某些炎症细胞因子可促进妊娠期滋养细胞促肾上腺皮质激素释放激素（CRH）的表达，胎盘CRH可诱导人促肾上腺皮质激素（ACTH）的产生。然而，在啮齿动物胎盘中是否也是如此仍不清楚。在这项研究中，我们研究了促炎细胞因子LIF对诱导小鼠滋养层干细胞（mTSCs）CRH的影响。在分化过程中，mTSCs中CRH水平逐渐升高。在LIF补充后第3天和第5天，与未用LIF处理的那些相比，LIF处理的分化的mTSCs中的Crh表达显著增加。此外，培养基中的CRH浓度增加。此后，我们研究了LIF下游途径对分化的mTSCs中CRH诱导的贡献。LIF诱导的CRH上调可通过抑制PI 3 K/AKT和MAPK磷酸化而减弱，但不能通过抑制JAK/STAT 3而减弱。因此，在mTSCs中，LIF通过激活PI 3 K/AKT和MAPK途径而不是JAK/STAT 3途径增加Crh表达。本研究提示mTSC是研究胎盘CRH调控和功能的理想体外模型。(C)2019爱思唯尔公司All rights reserved.
Previous studies have shown that some inflammatory cytokines promote the expression of corticotropin releasing hormone (CRH) in trophoblasts during pregnancy and that placental CRH could induce the production of adrenocorticotropic hormone (ACTH) in humans. However, whether the same is true in rodent placenta remains unclear. In this study, we examined the effect of pro-inflammatory cytokine LIF on the induction of CRH in mouse trophoblast stem cells (mTSCs). During differentiation, the CRH levels in mTSCs gradually increased. On days 3 and 5 after LIF supplementation, Crh expression in the differentiated mTSCs was significantly increased with LIF treatment than those without LIF treatment. Moreover, the CRH concentration in the culture media increased. Thereafter, we examined the contribution of the downstream pathways of LIF to CRH induction in differentiated mTSCs. The LIF-induced upregulation of CRH was attenuated by inhibition of PI3K/AKT and MAPK phosphorylation but not by inhibition of JAK/STAT3. Therefore, in mTSCs, LIF increased Crh expression through activation of the PI3K/AKT and MAPK pathways but not by the JAK/STAT3 pathway. The present study suggests that mTSC is an ideal in vitro model for studying regulation and function of placental CRH. (C) 2019 Elsevier Inc. All rights reserved.