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首页> 外文期刊>Molecular and Cellular Biology >Differentiation of Trophoblast Giant Cells and Their Metabolic Functions Are Dependent on Peroxisome Proliferator-Activated Receptor β/δ
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Differentiation of Trophoblast Giant Cells and Their Metabolic Functions Are Dependent on Peroxisome Proliferator-Activated Receptor β/δ

机译：滋养层巨细胞的分化及其代谢功能取决于过氧化物酶体增殖物激活的受体β/δ。

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Mutation of the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) severely affects placenta development, leading to embryonic death at embryonic day 9.5 (E9.5) to E10.5 of most, but not all, PPARβ/δ-null mutant embryos. While very little is known at present about the pathway governed by PPARβ/δ in the developing placenta, this paper demonstrates that the main alteration of the placenta of PPARβ/δ-null embryos is found in the giant cell layer. PPARβ/δ activity is in fact essential for the differentiation of the Rcho-1 cells in giant cells, as shown by the severe inhibition of differentiation once PPARβ/δ is silenced. Conversely, exposure of Rcho-1 cells to a PPARβ/δ agonist triggers a massive differentiation via increased expression of 3-phosphoinositide-dependent kinase 1 and integrin-linked kinase and subsequent phosphorylation of Akt. The links between PPARβ/δ activity in giant cells and its role on Akt activity are further strengthened by the remarkable pattern of phospho-Akt expression in vivo at E9.5, specifically in the nucleus of the giant cells. In addition to this phosphatidylinositol 3-kinase/Akt main pathway, PPARβ/δ also induced giant cell differentiation via increased expression of I-mfa, an inhibitor of Mash-2 activity. Finally, giant cell differentiation at E9.5 is accompanied by a PPARβ/δ-dependent accumulation of lipid droplets and an increased expression of the adipose differentiation-related protein (also called adipophilin), which may participate to lipid metabolism and/or steroidogenesis. Altogether, this important role of PPARβ/δ in placenta development and giant cell differentiation should be considered when contemplating the potency of PPARβ/δ agonist as therapeutic agents of broad application.
机译：核受体过氧化物酶体增殖物激活的受体β/δ（PPARβ/δ）的突变严重影响胎盘发育，导致大多数（但不是全部）PPARβ/δ在胚胎9.5（E9.5）至E10.5时死亡。 -无效的突变体胚胎。虽然目前对发育中的胎盘中PPARβ/δ调控的途径了解甚少，但本文证明了PPARβ/δ无效胚的胎盘的主要改变是在巨细胞层中发现的。实际上，PPARβ/δ活性对于巨细胞中Rcho-1细胞的分化必不可少，如PPARβ/δ沉默后对分化的严重抑制所示。相反，Rcho-1细胞暴露于PPARβ/δ激动剂会通过增加3-磷酸肌醇依赖性激酶1和整合素连接的激酶的表达以及随后Akt的磷酸化来引发大规模分化。巨细胞中PPARβ/δ活性与其对Akt活性的作用之间的联系通过体内在E9.5，特别是在巨细胞核中的磷酸化Akt表达的显着模式而得到进一步加强。除了该磷脂酰肌醇3-激酶/ Akt主途径外，PPARβ/δ还通过增加I-mfa（一种Mash-2活性的抑制剂）的表达来诱导巨细胞分化。最后，在E9.5时，巨大的细胞分化伴随着脂滴的PPARβ/δ依赖性积累和脂肪分化相关蛋白（也称为脂肪蛋白）的表达增加，这可能参与脂质代谢和/或类固醇生成。总之，在考虑PPARβ/δ激动剂作为广泛应用的治疗剂的效力时，应考虑PPARβ/δ在胎盘发育和巨细胞分化中的重要作用。

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