Malic enzyme 1 is important for uterine decidualization in response to progesterone/cAMP/PKA/HB‐EGF pathway
Malic enzyme 1 is important for uterine decidualization in response to progesterone/cAMP/PKA/HB‐EGF pathway
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DOI：
10.1096/fj.201902289r
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
Hai-Fan Yu;Cui-Cui Duan-Cui;Zhan‐Qing Yang;Yu‐Si Wang;Z. Yue;B. Guo
中科院分区：
文献类型：
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作者：
Hai-Fan Yu;Cui-Cui Duan-Cui;Zhan‐Qing Yang;Yu‐Si Wang;Z. Yue;B. Guo
苹果酸酶1（Malic enzyme 1，Me 1）是参与糖酵解途径和柠檬酸循环的苹果酸酶，对维持细胞内氧化还原平衡和能量代谢至关重要，但其在子宫蜕膜化中的生理作用及其调控机制尚不清楚。目前的研究表明，Me 1在子宫蜕膜细胞中有强表达，并能促进间质细胞的增殖和分化，加速细胞周期转换，提示Me 1在子宫蜕膜化过程中具有重要作用。沉默Me 1减弱了NADPH的产生并降低了GR活性，而加入NADPH改善了Me 1缺失引起的GR活性缺陷。进一步分析发现，Me 1通过GR调节细胞内GSH含量，同时，Me 1在维持线粒体功能方面发挥作用，这表明Me 1的阻断导致线粒体O2-水平的积累、ATP产生的减少和线粒体DNA拷贝数的减少，并伴有线粒体膜电位的缺陷。在子宫基质细胞中，孕酮通过PR-cAMP-PKA途径诱导Me 1表达。HB-EGF的敲低可能会阻碍孕酮和cAMP对Me 1的调节。总的来说，Me 1是响应孕酮/cAMP/PKA/HB-EGF途径的子宫蜕膜化所必需的，并在预防线粒体功能障碍中起重要作用。
Malic enzyme 1 (Me1), a member of the malic enzymes involving in glycolytic pathway and citric acid cycle, is essential for the energy metabolism and maintenance of intracellular redox balance state, but its physiological role and regulatory mechanism in the uterine decidualization are still unknown. Current study showed that Me1 was strongly expressed in decidual cells, and could promote the proliferation and differentiation of stromal cells followed by an accelerated cell cycle transition, indicating an importance of Me1 in the uterine decidualization. Silencing of Me1 attenuated NADPH generation and reduced GR activity, while addition of NADPH improved the defect of GR activity elicited by Me1 depletion. Further analysis found that Me1 modulated intracellular GSH content via GR. Meanwhile, Me1 played a role in maintaining mitochondrial function as indicated by these observations that blockadge of Me1 led to the accumulation of mitochondrial O2- level and decreased ATP production and mtDNA copy numbers accompanied with defective mitochondrial membrane potential. In uterine stromal cells, progesterone induced Me1 expression through PR‐cAMP‐PKA pathway. Knockdown of HB‐EGF might impede the regulation of progesterone and cAMP on Me1. Collectively, Me1 is essential for uterine decidualization in response to progesterone/cAMP/PKA/HB‐EGF pathway and plays an important role in preventing mitochondrial dysfunction.