Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts.

Cross-talk between cAMP and MAPK pathways in HSD11B2 induction by hCG in placental trophoblasts.
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胎盘滋养层 hCG 诱导 HSD11B2 过程中 cAMP 和 MAPK 通路之间的交互作用

DOI:
10.1371/journal.pone.0107938
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Sun K
Sun K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shu Q;Li W;Li J;Wang W;Liu C;Sun K

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胎儿在​​妊娠期间过度接触糖皮质激素不利于胎儿发育。母体糖皮质激素进入胎儿循环是由胎盘合体滋养细胞中的 2 型 11β-羟基类固醇脱氢酶 (HSD11B2) 控制的。人绒毛膜促性腺激素 (hCG) 通过激活 cAMP 通路在维持胎盘 HSD11B2 表达方面发挥重要作用。在本研究中,我们研究了 hCG 激活 cAMP 通路与随后细胞外信号调节激酶 1/2 (ERK1/2) 或 p38 丝裂原激活蛋白激酶 (MAPK) 通路磷酸化在调节人胎盘合体滋养层胎盘 HSD11B2 表达中的关系。我们发现用 hCG 或二丁基 cAMP (dbcAMP) 处理胎盘合体滋养层可以促进 p38 和 ERK1/2 的磷酸化。用 SB203580 抑制 p38 MAPK 不仅降低了基础 HSD11B2 mRNA 和蛋白质水平,而且还减弱了 hCG 或 dbcAMP 诱导的 HSD11B2 水平。相比之下,用 PD98059 抑制 ERK1/2 会增加 HSD11B2 的基础 mRNA 和蛋白质水平,并且对 hCG 或 dbcAMP 诱导的 HSD11B2 mRNA 和蛋白质水平没有影响。这些数据表明p38 MAPK参与HSD11B2的基础表达和hCG/cAMP诱导的HSD11B2表达,并且ERK1/2可能至少在人胎盘合体滋养层HSD11B2的基础表达中发挥与p38 MAPK相反的作用,并且hCG/cAMP和MAPK级联在胎盘HSD11B2表达的调节中存在复杂的串扰。
Overexposure of the fetus to glucocorticoids in gestation is detrimental to fetal development. The passage of maternal glucocorticoids into the fetal circulation is governed by 11beta-Hydroxysteroid Dehydrogenase Type 2 (HSD11B2) in the placental syncytiotrophoblasts. Human chorionic gonadotropin (hCG) plays an important role in maintaining placental HSD11B2 expression via activation of the cAMP pathway. In this study, we investigated the relationship between the activation of the cAMP pathway by hCG and subsequent phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) or p38 mitogen-activated protein kinase (MAPK) pathways in the regulation of placental HSD11B2 expression in human placental syncytiotrophoblasts. We found that treatment of the placental syncytiotrophoblasts with either hCG or dibutyl cAMP (dbcAMP) could promote the phosphorylation of p38 and ERK1/2. Inhibition of p38 MAPK with SB203580 not only reduced the basal HSD11B2 mRNA and protein levels but also attenuated HSD11B2 levels induced by either hCG or dbcAMP. By contrast, inhibition of ERK1/2 with PD98059 increased the basal mRNA and protein levels of HSD11B2 and had no effect on HSD11B2 mRNA and protein levels induced by either hCG or dbcAMP. These data suggest that p38 MAPK is involved in both basal and hCG/cAMP-induced expression of HSD11B2, and ERK1/2 may play a role opposite to p38 MAPK at least in the basal expression of HSD11B2 in human placental syncytiotrophoblasts and that there is complicated cross-talk between hCG/cAMP and MAPK cascades in the regulation of placental HSD11B2 expression.
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