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Open AccessArticle

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

Department of Pediatrics, Osaka Medical College, Osaka 569-8686, Japan
Department of Pediatrics, Osaka Rosai Hospital, Osaka 591-8025, Japan
Department of Medicine, Shinseikai Daiichi Hospital, Aichi 468-0031, Japan
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3337;
Received: 2 August 2018 / Revised: 19 October 2018 / Accepted: 23 October 2018 / Published: 26 October 2018
(This article belongs to the Special Issue Molecular Biology of Nuclear Receptors)
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. View Full-Text
Keywords: cholestasis; retinol; bile acid; farnesoid X receptor cholestasis; retinol; bile acid; farnesoid X receptor
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MDPI and ACS Style

Takitani, K.; Kishi, K.; Miyazaki, H.; Koh, M.; Tamaki, H.; Inoue, A.; Tamai, H. Altered Expression of Retinol Metabolism-Related Genes in an ANIT-Induced Cholestasis Rat Model. Int. J. Mol. Sci. 2018, 19, 3337.

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