Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes

被引：101

作者：

Langhi, Cedric ^{[1
,2
]}

Le May, Cedric ^{[1
,2
]}

Kourimate, Sanae ^{[1
,2
]}

Caron, Sandrine ^{[4
,5
,6
]}

Staels, Bart ^{[4
,5
,6
]}

Krempf, Michel ^{[1
,2
,3
]}

Costet, Philippe ^{[1
,2
]}

Cariou, Bertrand ^{[1
,2
,3
]}

机构：

[1] CHU Hotel Dieu, INSERM, U915, NORD 3, F-44000 Nantes, France

[2] Univ Nantes, Fac Med, Inst Thorax, F-44000 Nantes, France

[3] CHU Nantes, Div Endocrinol Maladies Metab & Nutr, Inst Thorax, F-44000 Nantes, France

[4] Inst Pasteur, Dept Atherosclerose, F-59019 Lille, France

[5] INSERM, U545, F-59019 Lille, France

[6] Univ Lille 2, Fac Pharm, Fac Med, F-59006 Lille, France

来源：

FEBS LETTERS | 2008年 / 582卷 / 06期

关键词：

PCSK9; bile acid; FXR; statin; LDL-cholesterol;

D O I：

10.1016/j.febslet.2008.02.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The purpose of this study was to determine whether bile acids (BAs) modulate hepatic pro-protein convertase subtilisin/kexin 9 (PCSK9) gene expression. Immortalized human hepatocytes were treated with various BAs. Chenodeoxycholic acid (CDCA) treatment specifically decreased both PCSK9 mRNA and protein contents. Moreover, activation of the BA-activated farnesoid X receptor (FXR) by its synthetic specific agonist GW4064 also decreased PCSK9 expression. Of functional relevance, coadministration of CDCA counteracted the statin-induced PCSK9 expression, leading to a potentiation of LDL receptor activity. This study suggests that a transcriptional repression of PCSK9 by CDCA or FXR agonists may potentiate the hypolipidemic effect of statins. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：949 / 955

页数：7

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