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Hepatic CBP/p300 maintain bile acid homeostasis through histone acetylation-mediated KLF10-BSEP axis
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DOI：10.1016/j.jcmgh.2026.101828.png)
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Abstract
En 中文
Disruption of bile acid metabolism contributes to various liver diseases. Although CBP/p300 are known regulators of hepatic metabolism, their role in bile acid homeostasis remains elusive.
Keywords:
CBP/p300
Bile acid metabolism
BSEP
KLF10
Histone acetylation
Cholestasis
Abcb11
ATP binding cassette subfamily B member 11
Abcc2
ATP binding cassette subfamily C member 2
Abcc3
ATP binding cassette subfamily C member 3
Abcc4
ATP binding cassette subfamily C member 4
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANOVA
one-way analysis of variance
AST
aspartate aminotransferase
BAGs
bile acid-associated genes
BAs
bile acids
BRIC2
benign recurrent intrahepatic cholestasis type 2
BSEP
bile salt export pump
CA
cholic acid
CBP
CREB binding protein
CDCA
chenodeoxycholic acid
ChIP
Chromatin immunoprecipitation
ChIP-qPCR
Chromatin Immunoprecipitation-quantitative Polymerase Chain Reaction
Cyp27a1
Cytochrome P450 family 27 subfamily A member 1
Cyp7a1
Cytochrome P450 family 7 subfamily A member 1
Cyp8b1
Cytochrome P450 family 8 subfamily B member 1
DBil
direct bilirubin
DDC
3,5-diethoxycarbonyl-1,4-dihydrocollidine
DEGs
differentially expressed genes
FBS
fetal bovine serum
FXR
farnesoid X receptor
GCA
glycocholic acid
GCDCA
glycodeoxycholic acid
GSEA
Gene Set Enrichment Analysis
HATs
histone acetyltransferases
HDACs
histone deacetylases
ICP
intrahepatic cholestasis of pregnancy
IGV
Integrative Genomics Viewer
KLF10
Kruppel-like transcription factor 10
LC-MS
liquid chromatographymass spectrometry
LRH-1
Liver receptor homolog-1
MCRS1
Microspherule Protein 1
MRP2
multidrug resistance-associated protein 2
MRP3
multidrug resistance-associated protein 3
MRP4
multidrug resistance-associated protein 4
NASH
non-alcoholic steatohepatitis
NC
negtive control
Nr0b2
Nuclear receptor subfamily 0 group B member 2
Nr1h4
nuclear receptor subfamily 1 group H member 4
NTCP
sodium taurocholate cotransporting polypeptide
OATP1A1
organic anion transporting polypeptide 1A1
OSTα
organic solute transporter alpha
OSTβ
encoding organic solute transporter beta
p300
E1A binding protein p300
PCA
principal component analysis
PFIC2
progressive familial intrahepatic cholestasis type 2
RNA-seq
RNA sequencing
RT-qPCR
real-time quantitative PCR
SEM
standard error of the mean
Slc10a1
solute carrier family 10 member 1
Slc51a
solute carrier family 51 subunit alpha
Slc51b
solute carrier family 51 subunit beta
Slco1a1
solute carrier organic anion transporter family member 1a1
SPF
specific-pathogen-free
TBA
total bile acid
TBG
thyroxine-binding globulin
TBil
total bilirubin
TCA
taurocholic acid
TCDCA
taurochenodeoxycholic acid
TGFβ
transforming growth factor β
TSS
transcription start site
TUDCA
tauroursodeoxycholic acid
Tα/βMCA
tauro-α/β-muricholic acid
WT
wild type
γ-GT
γ-glutamyltransferase
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