Comparison of phenotypic and global gene expression changes in Xenopus tropicalis embryos induced by agonists of RAR and RXR
Comparison of phenotypic and global gene expression changes in Xenopus tropicalis embryos induced by agonists of RAR and RXR
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RAR 和 RXR 激动剂诱导的热带爪蟾胚胎表型和整体基因表达变化的比较
DOI：
10.1016/j.taap.2017.07.004
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发表时间：
2017-09
影响因子：
3.8
通讯作者：
Shi Huahong
中科院分区：
文献类型：
--
作者：
Zhu Jingmin;Hu Lingling;Li Lingyun;Huang Xiao;Shi Huahong
视黄酸通过两类受体发挥作用，即视黄酸受体 (RAR) 和类视黄酸 X 受体 (RXR)。然而，RAR 和 RXR 之间的作用差异尚未明确。在本研究中，我们比较研究了三种不同激动剂诱导的热带非洲爪蟾胚胎的表型和整体基因表达变化，包括RAR选择性配体（全反式维甲酸，at-RA）、RXR选择性配体（氟贝沙罗汀，FBA）及其共同配体（9-顺维甲酸，9c-RA）。所有三种激动剂均在 X 中诱导了显着且相似的畸形。浓度为 5–50 µg/L 的热带胚胎。特别是前部结构和尾部区域的发育发生了巨大的改变。表型和基因谱的层次聚类分析表明，9c-RA 诱导的效应与 at-RA 和 FBA 诱导的效应不同。上调基因涉及多个通路，而下调基因主要与光转导和酪氨酸代谢有关。 at-RA 主要影响视黄醇、糖酵解、淀粉和蔗糖代谢，而 FBA 会导致更广泛的途径紊乱，例如 PPAR、脂肪细胞因子、胰岛素、FoxO 信号途径、丙氨酸、天冬氨酸和谷氨酸代谢。 RXR 是其他几种核受体的异二聚体伙伴，这开启了 FBA（例如 RXR-PPAR）介导其他类维生素A作用的可能性。我们的数据表明，不仅 RXR-RAR，而且 RXR-PPAR 在 X 类维生素A治疗的代谢控制中发挥着重要作用。热带胚胎。
Retinoic acid functions through two classes of receptors, i.e., the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). The difference in the role between RAR and RXR, however, are not well clarified. In the present study, we comparatively investigated the phenotypic and global gene expression changes in Xenopus tropicalis embryos induced by three different agonists, including a RAR selective ligand (all-transretinoic acid, at-RA), a RXR selective ligand (fluorobexarotene, FBA) and their common ligand (9-cisretinoic acid, 9c-RA). All three agonists induced striking and similar malformations inX. tropicalisembryos at the concentrations of 5–50 μg/L. Especially, the development of anterior structures and caudal region was dramatically altered. The hierarchical clustering analysis of phenotypes and gene profiles suggested that effects induced by 9c-RA separated from those by at-RA and FBA. The up-regulated genes were involved in multiple pathways while down-regulated genes were mainly related to phototransduction and tyrosine metabolism. at-RA primarily affected the retinol, glycolysis, starch and sucrose metabolisms while FBA led to disturbances in more wide-ranging pathways such as the PPAR, adipocytokine, insulin, FoxO signaling pathways, alanine, aspartate and glutamate metabolism. RXR is a heterodimeric partner for several other nuclear receptors, which opens the possibility that additional retinoid effects could be mediated by FBA, such as RXR-PPAR. Our data indicates that not only RXR-RAR but also RXR-PPAR plays important roles in the control of metabolism with retinoid treatment inX. tropicalisembryos.
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影响因子：
11.2
作者：
C. Di;S. Liao;D. C. Adamson;T. Parrett;D. Broderick;Qun Shi;C. Lengauer;Jordan M. Cummins;V. V
通讯作者：
C. Di;S. Liao;D. C. Adamson;T. Parrett;D. Broderick;Qun Shi;C. Lengauer;Jordan M. Cummins;V. V
影响因子：
2.6
作者：
Bertwistle, D;Walmsley, ME;Patient, RK
通讯作者：
Patient, RK
影响因子：
4.6
作者：
P. Franco;A. Paganelli;S. López;A. Carrasco
通讯作者：
P. Franco;A. Paganelli;S. López;A. Carrasco
影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
影响因子：
10.5
作者：
Abu-Abed, S;Dollé, P;Petkovich, M
通讯作者：
Petkovich, M