Retinoic acid regulates cell cycle genes and accelerates normal mouse liver regeneration.
Retinoic acid regulates cell cycle genes and accelerates normal mouse liver regeneration.
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DOI：
10.1016/j.bcp.2014.07.003
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发表时间：
2014-09-15
影响因子：
5.8
通讯作者：
Wan YJ
中科院分区：
文献类型：
--
作者：
Liu HX;Ly I;Hu Y;Wan YJ
全反式维甲酸（RA）是一种有效的再生诱导剂。由于肝脏是维生素A储存和生物活化的主要场所，因此本研究检测了RA在小鼠肝细胞增殖和肝再生中的作用。通过经口灌胃接受单剂量RA（25 μg/g）的小鼠出现肝肿大，Ki 67阳性细胞数量增加，并诱导肝脏中细胞周期基因的表达。DNA结合数据显示，RA受体维甲酸受体β（RARβ）和维甲酸x受体α（RXRα）与细胞周期基因Cdk 1、Cdk 2、Cyclin B、Cyclin E和Cdc 25 a结合。此外，RA处理诱导RARβ/RXRα与Cdk 1、Cdk 2、Cyclin D和Cdk 6基因的新型结合。RARβ/RXRα结合位点均含有AGGTCA样基序。RA治疗还促进部分肝切除术（PH）后的肝再生。RA信号转导与正常肝再生有关，因为RARβ、Aldh 1a 2、Crabp 1和Crbp 1的mRNA水平在PH后1.5天的肝细胞增殖的活跃期都被诱导。PH前RA治疗导致RARβ、Aldh 1a 2、Crabp 1和Crbp 1的早期上调，伴随着细胞周期基因的早期诱导。RARβ、c-myc、Cyclin D、E和A的Western印迹进一步支持RA处理对类维生素A信号和细胞增殖的早期诱导。综上所述，我们的数据表明，RA可以调节细胞周期进程，加速肝再生。这种作用与RA信号传导的早期诱导有关，其包括类维生素A的受体、结合蛋白和加工酶的表达增加。
All-trans retinoic acid (RA) is a potent inducer of regeneration. Because the liver is the principal site for storage and bioactivation of vitamin A, the current study examines the effect of RA in mouse hepatocyte proliferation and liver regeneration. Mice that received a single dose of RA (25 μg/g) by oral gavage developed hepatomegaly with increased number of Ki67-positive cells and induced expression of cell cycle genes in the liver. DNA binding data revealed that RA receptors retinoic acid receptor β (RARβ) and retinoid x receptor α (RXRα) bound to cell cycle genes Cdk1, Cdk2, Cyclin B, Cyclin E, and Cdc25a in mice with and without RA treatment. In addition, RA treatment induced novel binding of RARβ/RXRα to Cdk1, Cdk2, Cyclin D, and Cdk6 genes. All RARβ/RXRα binding sites contained AGGTCA-like motifs. RA treatment also promoted liver regeneration after partial hepatectomy (PH). RA signaling was implicated in normal liver regeneration as the mRNA levels of RARβ, Aldh1a2, Crabp1, and Crbp1 were all induced 1.5 days after PH during the active phase of hepatocyte proliferation. RA treatment prior to PH resulted in early up-regulation of RARβ, Aldh1a2, Crabp1, and Crbp1, which was accompanied by an early induction of cell cycle genes. Western blotting for RARβ, c-myc, Cyclin D, E, and A further supported the early induction of retinoid signal and cell proliferation by RA treatment. Taken together, our data suggest that RA may regulate cell cycle progression and accelerates liver regeneration. Such effect is associated with an early induction of RA signaling, which includes increased expression of the receptor, binding proteins, and processing enzyme for retinoids.
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影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
4.7
作者：
Ledda-Columbano, GM;Pibiri, M;Columbano, A
通讯作者：
Columbano, A
影响因子：
13.5
作者：
Falasca, L;Favale, A;Devirgiliis, LC
通讯作者：
Devirgiliis, LC
影响因子：
4.2
作者：
Chae, Jung-Il;Jeon, Young-Joo;Shim, Jung-Hyun
通讯作者：
Shim, Jung-Hyun
DOI：
10.1073/pnas.1011845108
发表时间：
2011-01-11
影响因子：
11.1
作者：
Liu, Xingxing;Nugoli, Melanie;Giguere, Vincent
通讯作者：
Giguere, Vincent