Cross talk between cAMP and p38 MAPK pathways in the induction of leptin by hCG in human placental syncytiotrophoblasts
Cross talk between cAMP and p38 MAPK pathways in the induction of leptin by hCG in human placental syncytiotrophoblasts
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DOI：
10.1530/rep-11-0053
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发表时间：
2011-08-01
期刊：
影响因子：
3.8
通讯作者：
Sun, K.
中科院分区：
文献类型：
--
作者：
Ge, Y. C.;Li, J. N.;Sun, K.
胎盘合体滋养层细胞产生的瘦素参与妊娠过程中的许多过程，包括着床、细胞滋养层细胞增殖和营养物质通过胎盘的转移。尽管瘦素在妊娠中的功能意义，瘦素合成的调节在人类胎盘合体滋养细胞中知之甚少。在这项研究中，我们调查的作用，内源性人绒毛膜促性腺激素（hCG）在调节瘦素的生产，以及涉及cAMP和p38丝裂原活化蛋白激酶（MAPK）通路之间的串扰的潜在机制。我们发现，中和内源性hCG与其抗体剂量依赖性地降低瘦素mRNA水平和分泌，而外源性hCG增加瘦素mRNA水平和分泌。用二丁酰cAMP（db cAMP）或毛喉素激活cAMP途径，重现了hCG对瘦素表达的刺激作用。用H89抑制蛋白激酶A不仅降低了基础瘦素表达，而且减弱了hCG诱导的瘦素表达。用db cAMP和hCG磷酸化的p38 MAPK处理合胞体滋养层。用SB 203580抑制p38 MAPK不仅降低了基础瘦素的产生，而且减弱了hCG和db cAMP诱导的瘦素产生。这些数据表明，内源性hCG在维持人胎盘合体滋养层细胞的瘦素产生中起着重要作用，这种作用涉及cAMP和p38 MAPK通路之间的串扰。生殖（2011年）142 369-375
Leptin produced by the placental syncytiotrophoblasts participates in a number of processes in pregnancy including implantation, proliferation of the cytotrophoblasts, and nutrient transfer across the placenta. Despite the functional significance of leptin in pregnancy, the regulation of leptin synthesis is poorly understood in human placental syncytiotrophoblasts. In this study, we investigated the role of endogenous human chorionic gonadotropin (hCG) in the regulation of leptin production as well as the underlying mechanism involving the cross talk between cAMP and p38 mitogen-activated protein kinase (MAPK) pathways. We found that neutralization of endogenous hCG with its antibody dose dependently decreased leptin mRNA level and secretion, whereas exogenous hCG increased leptin mRNA level and secretion. Activation of the cAMP pathway with dibutyryl cAMP (db cAMP) or forskolin recapitulated the stimulatory effect of hCG on leptin expression. Inhibition of protein kinase A with H89 not only reduced the basal leptin expression but also attenuated the induced leptin expression by hCG. Treatment of the syncytiotrophoblasts with db cAMP and hCG phosphorylated p38 MAPK. Inhibition of p38 MAPK with SB203580 not only reduced the basal leptin production but also attenuated the leptin-induced production by both hCG and db cAMP. These data suggest that endogenous hCG plays a significant role in maintaining leptin production in human placental syncytiotrophoblasts, and this effect involves a cross talk between cAMP and p38 MAPK pathways. Reproduction (2011) 142 369-375