Altered Expression of Retinol Metabolism-Related Genes in an ANIT-Induced Cholestasis Rat Model.

Altered Expression of Retinol Metabolism-Related Genes in an ANIT-Induced Cholestasis Rat Model.
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DOI:
10.3390/ijms19113337
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发表时间:
2018-10-26
影响因子:
5.6
通讯作者:
Tamai H
Tamai H
中科院分区:
生物学2区
文献类型:
--
作者:
Takitani K;Kishi K;Miyazaki H;Koh M;Tamaki H;Inoue A;Tamai H

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胆汁淤积被定义为由胆汁形成功能障碍引起的胆汁分泌减少。肠道内胆汁分泌不足会破坏胶束的形成,从而可能导致脂质和脂溶性维生素的吸收减少。在这里,我们研究了视黄醇稳态和视黄醇代谢相关基因的改变,包括β-胡萝卜素15,15'单加氧酶(BCMO)、卵磷脂:视黄醇酰基转移酶(LRAT)、乙醛脱氢酶(ALDH)、细胞色素P450 26A1(CYP26A1)和视黄酸受体(RAR)β。 α-萘基异硫氰酸酯(ANIT)诱导的胆汁淤积大鼠模型。此外,我们检查了法尼醇 X 受体 (FXR) 靶基因的表达。我们的结果表明,与对照大鼠相比,ANIT 大鼠的血浆视黄醇水平降低。相反,两组之间的肝脏视黄醇水平没有差异。胆汁淤积模型大鼠肝脏和肠道中FXR靶基因的表达受到抑制。与对照大鼠相比,ANIT 大鼠肝脏中的 BCMO 表达减少,肠道中的表达增加。最后,与对照大鼠相比,胆汁淤积大鼠的肝脏 LRAT、RARβ 和 ALDH1A1 表达降低,而肝脏 CYP26A1 表达没有改变。胆汁淤积模型大鼠肠道 BCMO 表达的增加可能补偿循环视黄醇水平的降低。 BCMO 表达可能以组织特异性方式进行调节,以维持视黄醇的稳态。
Cholestasis is defined as a reduction of bile secretion caused by a dysfunction of bile formation. Insufficient bile secretion into the intestine undermines the formation of micelles, which may result in the reduced absorption of lipids and fat-soluble vitamins. Here, we investigated the retinol homeostasis and the alterations of retinol metabolism-related genes, including β-carotene 15,15′ monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), cytochrome P450 26A1 (CYP26A1), and retinoic acid receptors (RAR) β, in a α-naphthyl isothiocyanate (ANIT)-induced cholestasis rat model. Moreover, we examined the expression of the farnesoid X receptor (FXR) target genes. Our results showed that plasma retinol levels were decreased in ANIT rats compared to control rats. On the contrary, hepatic retinol levels were not different between the two groups. The expression of FXR target genes in the liver and intestine of cholestasis model rats was repressed. The BCMO expression was decreased in the liver and increased in the intestine of ANIT rats compared to control rats. Finally, the hepatic expression of LRAT, RARβ, and ALDH1A1 in cholestatic rats was decreased compared to the control rats, while the CYP26A1 expression of the liver was not altered. The increased expression of intestinal BCMO in cholestasis model rats might compensate for decreased circulatory retinol levels. The BCMO expression might be regulated in a tissue-specific manner to maintain the homeostasis of retinol.
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