Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially
10.1016/j.apsb.2020.11.021
- Author:
Yue GAO
1
;
Shicheng FAN
1
;
Hua LI
2
;
Yiming JIANG
1
;
Xinpeng YAO
1
;
Shuguang ZHU
2
;
Xiao YANG
1
;
Ruimin WANG
1
;
Jianing TIAN
1
;
Frank J GONZALEZ
3
;
Min HUANG
1
;
Huichang BI
1
Author Information
1. Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
2. Department of Hepatic Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510006, China.
3. Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
- Publication Type:Journal Article
- Keywords:
ALB, albumin;
ALP, alkaline phosphatase;
ALT, alanine aminotransferase;
ANKRD1, ankyrin repeat domain 1;
AST, aspartate transaminase;
AhR, aryl hydrocarbon receptor;
CAR, constitutive androstane receptor;
CCNA1, cyclin A1;
CCND1, cyclin D1;
CCNE1, cyclin E1;
CITCO, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime;
CTGF, connective tissue growth factor;
CTNNB1, β-catenin;
CV, central vein;
CYR61, cysteine-rich angiogenic inducer 61;
Co-IP, co-immunoprecipitation;
Constitutive androstane receptor;
EGFR, epidermal growth factor receptor;
FOXM1, forkhead box M1;
FXR, farnesoid X receptor;
H&E, haematoxylin and eosin;
Hepatomegaly;
Liver enlargement;
Liver regeneration;
Nuclear receptors;
PHx, partial hepatectomy;
PPARα, peroxisome proliferators-activated receptor alpha;
PV, portal vein;
Partial hepatectomy;
Protein–protein interaction;
TBA, total bile acid;
TBIL, total bilirubin;
TCPOBOP, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene;
TEAD, TEA domain family member;
YAP, yes-associated protein;
Yes-associated protein
- From:
Acta Pharmaceutica Sinica B
2021;11(3):727-737
- CountryChina
- Language:English
-
Abstract:
The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67
