Fine-Tuning of Sirtuin 1 Expression Is Essential to Protect the Liver From Cholestatic Liver Disease.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Britt A BlokkerNaiara Beraza

Abstract

Cholestasis comprises aetiologically heterogeneous conditions characterized by accumulation of bile acids in the liver that actively contribute to liver damage. Sirtuin 1 (SIRT1) regulates liver regeneration and bile acid metabolism by modulating farnesoid X receptor (FXR); we here investigate its role in cholestatic liver disease. We determined SIRT1 expression in livers from patients with cholestatic disease, in two experimental models of cholestasis, as well as in human and murine liver cells in response to bile acid loading. SIRT1-overexpressing (SIRToe ) and hepatocyte-specific SIRT1-KO (knockout) mice (SIRThep-/- ) were subjected to bile duct ligation (BDL) and were fed with a 0.1% DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) diet to determine the biological relevance of SIRT1 during cholestasis. The effect of NorUDCA (24-norursodeoxycholic acid) was tested in BDL/SIRToe mice. We found that SIRT1 was highly expressed in livers from cholestatic patients, mice after BDL, and Mdr2 knockout mice (Mdr2-/- ) animals. The detrimental effects of SIRT1 during cholestasis were validated in vivo and in vitro. SIRToe mice showed exacerbated parenchymal injury whereas SIRThep-/- mice evidenced a moderate improvement after BDL and 0...Continue Reading

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Citations

Apr 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gang LiuSimon Keely
Aug 25, 2019·Scientific Reports·Raul Cabrera-RubioNaiara Beraza
Jul 24, 2020·JCI Insight·Lihua HaoByung-Hyun Park
Dec 31, 2019·Seminars in Liver Disease·Claudio PintoLuca Maroni
Feb 11, 2020·Frontiers in Medicine·Claudio PintoMarco Marzioni
Apr 13, 2019·Wiener klinische Wochenschrift·Claudia D Fuchs-Steiner
May 16, 2019·Journal of Zhejiang University. Science. B·Li-Hua JinWen-Dong Huang
Mar 14, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anna Isaacs-TenNaiara Beraza
Jun 1, 2021·Chemico-biological Interactions·Fatemeh Alaei FaradonbehStanislav Micuda
Dec 25, 2021·Cellular and Molecular Gastroenterology and Hepatology·Anna Isaacs-TenNaiara Beraza

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Methods Mentioned

BETA
ubiquitination
biopsy
biopsies
transfection
FACS
ELISA
acetylation

Software Mentioned

ImageLab
Frida
Image Lab
Graph Pad Prism

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