Regulation of cyp26a1 on Th17 cells in mouse peri-implantation.
Regulation of cyp26a1 on Th17 cells in mouse peri-implantation.
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cyp26a1 对小鼠着床期 Th17 细胞的调控
DOI：
10.1111/jcmm.12196
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发表时间：
2014-03
影响因子：
5.3
通讯作者：
Peng JP
中科院分区：
文献类型：
--
作者：
Liu HY;Chao H;Liu ZK;Xia HF;Song Z;Yang Y;Peng JP
细胞色素P450 26 A1（cyp 26 a1）在小鼠着床期子宫中表达。这种蛋白质的抑制与着床位点的减少密切相关，表明cyp 26 a1在妊娠中的特定作用，并引发了关于代谢酶如何产生这种独特结果的问题。为了探索cyp 26 a1的有效下游靶点，并证实cyp 26 a1在围着床期的作用是否依赖于其代谢底物维甲酸（RA），我们用构建好的cyp 26 a1基因疫苗对小鼠外周血、脾脏和子宫着床部位的变化进行了表征。流式细胞仪检测结果显示，实验组外周血和脾脏中CD 4 +RORγt+ Th 17细胞均明显增加。RORγt和IL-17的表达表现为Th 17细胞减少，cyp 26 a1表达受抑制。为了获得更大的确定性，构建了cyp 26 a1抗体阻断模型和RNA干扰模型，以确定精确的靶免疫细胞群。高效液相色谱分析结果显示cyp 26 a1基因疫苗免疫后子宫at-RA明显增加。通过检测基因疫苗免疫后围着床期子宫组织RARα蛋白水平的确定以及针对RARα的特异性激动剂和拮抗剂的研究均提示RARα可能是RA信号转导的主要受体。这些结果从另一个侧面为RA在cyp 26 a1调控中的信号传递作用提供了更多的证据。在这里，我们发现cyp 26 a1调节的Th 17细胞依赖于at-RA信号传导，该信号传导通过小鼠围着床期的RARα传递。
Cytochrome P450 26A1 (cyp26a1) is expressed in the mouse uterus during peri-implantation. The repression of this protein is closely associated with a reduction in implantation sites, suggesting a specific role for cyp26a1 in pregnancy and prompting questions concerning how a metabolic enzyme can generate this distinct outcome. To explore the effective downstream targets of cyp26a1 and confirm if its role in peri-implantation depends on its metabolic substrate RA (retinoic acid), we characterized the changes in the peripheral blood, spleen and uterine implantation sites using the cyp26a1 gene vaccine constructed before. Flow cytometry results showed a significant increase in CD4+RORγt+ Th17 cells in both the peripheral blood and spleen in the experimental group. The expression of RORγt and IL-17 presented the Th17 cells reduction in uterus followed by the suppression of cyp26a1 expression. For greater certainty, cyp26a1 antibody blocking model and RNA interference model were constructed to determine the precise target immune cell group. High performance liquid chromatography results showed a significant increase in uterine at-RA followed by the immunization of cyp26a1 gene vaccine. Both the ascertain by measuring RARα protein levels in peri-implantation uterus after gene vaccine immunization and researches using the specific agonist and antagonist against RARα suggested that RARα may be the main RA receptor for signal transduction. These results provided more evidence for the signal messenger role of RA in cyp26a1 regulation from the other side. Here, we showed that the cyp26a1-regulated Th17 cells are dependent on at-RA signalling, which is delivered through RARα in mouse peri-implantation.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
视黄酸代谢酶细胞色素 P450 26a1 (Cyp26a1) 对于着床至关重要：其在早期妊娠中的作用的功能研究
影响因子：
5.6
作者：
Han, Bing-Chen;Xia, Hong-Fei;Peng, Jing-Pian
通讯作者：
Peng, Jing-Pian
DOI：
10.1111/j.1600-0897.2010.00812.x
发表时间：
2010-07-01
影响因子：
3.6
作者：
Nakashima, Akitoshi;Ito, Mika;Saito, Shigeru
通讯作者：
Saito, Shigeru
DOI：
10.1111/j.1600-0897.2009.00771.x
发表时间：
2010-02-01
影响因子：
3.6
作者：
Nakashima, Akitoshi;Ito, Mika;Saito, Shigeru
通讯作者：
Saito, Shigeru
影响因子：
11.4
作者：
Fujii, H;Sato, T;Hamada, H
通讯作者：
Hamada, H