Gestational diabetes induces placental genes for chronic stress and inflammatory pathways
Gestational diabetes induces placental genes for chronic stress and inflammatory pathways
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DOI：
10.2337/diabetes.52.12.2951
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发表时间：
2003-12-01
期刊：
影响因子：
7.7
通讯作者：
Haugeul-de Mouzon, S
中科院分区：
文献类型：
--
作者：
Radaelli, T;Varastehpour, A;Haugeul-de Mouzon, S
需要胰岛素抵抗的生理状态来优先将母体营养物导向胎儿-胎盘单位，从而允许胎儿充分生长。当女性发生妊娠期糖尿病（GDM）时，胰岛素抵抗更加严重，破坏了宫内环境，导致胎儿发育加速，巨大儿风险增加。作为母亲和胎儿之间的天然界面，胎盘是这种环境变化的必然目标。然而，导致胎儿，新生儿和成人代谢损害的不平衡的分子基础还不清楚。我们报告说，妊娠期糖尿病elevenness主要的变化，胎盘基因的表达谱显着增加的标志物和介质的炎症。在435个转录可重复修改，应激激活和炎症反应的基因代表了最大的功能簇（18.5%的调控基因）。白细胞介素、瘦素和肿瘤坏死因子-α受体及其下游分子衔接子的上调表明了招募应激激活蛋白/c-Jun NH 2-末端激酶的途径的激活。细胞外基质成分和血管生成激活因子的转录激活表明胎盘的主要结构重组。因此，胎盘转录组成为糖尿病妊娠环境改变的主要靶点。这些基因为阐明炎症途径和GDM相关胰岛素抵抗之间的联系提供了基础。
A physiological state of insulin resistance is required to preferentially direct maternal nutrients toward the feto-placental unit, allowing adequate growth of the fetus. When women develop gestational diabetes mellitus (GDM), insulin resistance is more severe and disrupts the intrauterine milieu, resulting in accelerated fetal development with increased risk of macrosomia. As a natural interface between mother and fetus, the placenta is the obligatory target of such environmental changes. However, the molecular basis for the imbalance that leads to fetal, neonatal, and adult metabolic compromises is not well understood. We report that GDM elicits major changes in the expression profile of placental genes with a prominent increase in markers and mediators of inflammation. Within the 435 transcripts reproducibly modified, genes for stress-activated and inflammatory responses represented the largest functional cluster (18.5% of regulated genes). Upregulation of interleukins, leptin, and tumor necrosis factor-alpha receptors and their downstream molecular adaptors indicated an activation of pathways recruiting stress-activated protein/c-Jun NH2-terminal kinases. Transcriptional activation of extracellular matrix components and angiogenic activators pointed to a major structural reorganization of the placenta. Thus, placental transcriptome emerges as a primary target of the altered environment of diabetic pregnancy. The genes identified provide the basis to elucidate links between inflammatory pathways and GDM-associated insulin resistance.