Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines
Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines
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DOI：
10.1007/s00125-006-0194-7
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发表时间：
2006-06-01
期刊：
影响因子：
8.2
通讯作者：
Randeva, HS
中科院分区：
文献类型：
--
作者：
Chen, J;Tan, B;Randeva, HS
目的/假设：妊娠是一种胰岛素抵抗状态，与细胞因子水平升高和新陈代谢的深刻改变有关。血清脂联素是一种具有抗炎和胰岛素增敏特性的脂肪因子，已被证明在妊娠期糖尿病患者中较低，妊娠期糖尿病是一种比正常妊娠更严重的胰岛素抵抗状态。假设人胎盘是脂联素的来源，我们研究了其表达和分泌，以及脂联素及其受体的细胞因子的调节。方法：应用实时RT-PCR、放射免疫分析、蛋白质印迹、放射性配体结合和免疫荧光分析来证明胎盘脂联素的表达、分泌和功能。结果：在人足月胎盘中发现脂联素基因表达和蛋白，主要在合体滋养层中表达。外植体实验条件培养基的放射免疫分析显示胎盘可以在体外分泌脂联素。向转染脂联素受体 1 (ADIPOR1) 基因的 HEK-293 细胞中添加条件培养基改变了细胞外信号调节激酶 1/2 和 p38 丝裂原激活蛋白激酶的磷酸化状态，用脂联素抗体预吸收后，这种作用被消除。细胞因子，包括 TNF-α、IFN-γ、IL-6 和瘦素，差异调节胎盘脂联素受体以及脂联素基因表达和分泌。有趣的是，在妊娠期糖尿病女性的胎盘中，我们观察到脂联素 mRNA 显着下调，ADIPOR1 表达显着上调，ADIPOR2 表达不显着增加。结论/解释：我们的结果表明，人类胎盘产生并分泌脂联素，并且脂联素及其受体受到细胞因子的差异调节，并且其表达在患有妊娠期糖尿病的女性中发生改变。总的来说，我们的新数据表明脂联素可能在调整母胎界面的能量代谢中发挥作用。
Aims/hypothesis: Pregnancy, a state of insulin resistance, is associated with elevated levels of cytokines and profound alterations in metabolism. Serum adiponectin, an adipokine with anti-inflammatory and insulin-sensitising properties, has been shown to be lower in patients with gestational diabetes mellitus, a state of greater insulin resistance than normal pregnancies. Hypothesising that the human placenta is a source of adiponectin, we investigated its expression and secretion, and the regulation by cytokines of adiponectin and its receptors. Methods: Real-time RT-PCR, radioimmunoassay, Western blotting, radioligand binding and immunofluorescent analyses were applied to demonstrate the expression, secretion and functionality of placental adiponectin. Results: Adiponectin gene expression and protein were found in the human term placenta, with expression primarily in the syncytiotrophoblast. RIA of conditioned media from explant experiments revealed that the placenta can secrete adiponectin in vitro. Addition of conditioned media to HEK-293 cells transfected with the gene for adiponectin receptor-1 (ADIPOR1) altered the phosphorylation status of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase, an effect abolished after preabsorption with adiponectin antibody. Cytokines, including TNF-alpha, IFN-gamma, IL-6 and leptin, differentially modulated placental adiponectin receptors as well as adiponectin gene expression and secretion. Interestingly, in placentae from women with gestational diabetes mellitus, we observed significant downregulation of adiponectin mRNA, significant upregulation of ADIPOR1 expression, and a non-significant increase in ADIPOR2 expression. Conclusions/interpretation: Our results indicate that the human placenta produces and secretes adiponectin, and that adiponectin and its receptors are differentially regulated by cytokines and their expression altered in women with gestational diabetes mellitus. Collectively, our novel data suggest that adiponectin may play a role in adapting energy metabolism at the materno-fetal interface.