PMID- 27052460
OWN - NLM
STAT- MEDLINE
DCOM- 20170307
LR  - 20170817
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 91
IP  - 1
DP  - 2017 Jan
TI  - Upregulation of hydroxysteroid sulfotransferase 2B1b promotes hepatic oval cell 
      proliferation by modulating oxysterol-induced LXR activation in a mouse model of 
      liver injury.
PG  - 271-287
LID - 10.1007/s00204-016-1693-z [doi]
AB  - Hydroxysteroid sulfotransferase 2B1b (SULT2B1b) sulfates cholesterol and 
      oxysterols. Hepatic oval cells (HOCs), thought to be progenitor cells, can be 
      triggered in chemically injured livers. The present study focused on the role of 
      SULT2B1b in HOC proliferation after liver injury. Our experiments revealed that 
      the expression of SULT2B1b was increased dramatically in a chemical-induced liver 
      injury model, mainly in HOCs. Upon challenge with a hepatotoxic diet containing 
      0.1 % 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), SULT2B1(-/-) mice 
      presented alleviated liver injury and less HOC proliferation compared with 
      wild-type (WT) mice, and these findings were verified by serum analysis, 
      histopathology, immunofluorescence staining, RNA-seq, and Western blotting. HOCs 
      derived from SULT2B1(-/-) mice showed lower proliferative capability than those 
      from WT mice. SULT2B1b overexpression promoted growth of the WB-F344 hepatic oval 
      cell line, whereas SULT2B1b knockdown inhibited growth of these cells. The 
      IL-6/STAT3 signaling pathway also was promoted by SULT2B1b. Liquid chromatography 
      and mass spectrometry indicated that the levels of 22-hydroxycholesterol, 
      25-hydroxycholesterol, and 24,25-epoxycholesterol were higher in the DDC-injured 
      livers of SULT2B1(-/-) mice than in livers of WT mice. The above oxysterols are 
      physiological ligands of liver X receptors (LXRs), and SULT2B1b suppressed 
      oxysterol-induced LXR activation. Additional in vivo and in vitro experiments 
      demonstrated that LXR activation could inhibit HOC proliferation and the 
      IL-6/STAT3 signaling pathway, and these effects could be reversed by SULT2B1b. 
      Our data indicate that upregulation of SULT2B1b might promote HOC proliferation 
      and aggravate liver injury via the suppression of oxysterol-induced LXR 
      activation in chemically induced mouse liver injury.
FAU - Wang, Zhengyang
AU  - Wang Z
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China.
FAU - Yang, Xiaoming
AU  - Yang X
AD  - Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
FAU - Chen, Liang
AU  - Chen L
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China.
FAU - Zhi, Xiuling
AU  - Zhi X
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China.
FAU - Lu, Hanyu
AU  - Lu H
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China.
FAU - Ning, Yanxia
AU  - Ning Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China.
FAU - Yeong, Joe
AU  - Yeong J
AD  - Department of Pathology, Singapore General Hospital, Singapore, Singapore.
AD  - Agency for Science, Technology and Research (A *STAR), Singapore Immunology 
      Network (SIgN), Biopolis, Singapore, 138648, Singapore.
FAU - Chen, Sifeng
AU  - Chen S
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China.
FAU - Yin, Lianhua
AU  - Yin L
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China.
FAU - Wang, Xinhong
AU  - Wang X
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China. wangxh@shmu.edu.cn.
FAU - Li, Xiaobo
AU  - Li X
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Fudan University, Shanghai, 200032, China. xbli@fudan.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20160406
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (3,5-diethoxycarbonyl-1,4-dihydrocollidine)
RN  - 0 (Biomarkers)
RN  - 0 (Carcinogens)
RN  - 0 (Liver X Receptors)
RN  - 0 (Oxysterols)
RN  - 0 (Pyridines)
RN  - EC 2.8.2.- (SULT2B1b protein, mouse)
RN  - EC 2.8.2.- (Sulfotransferases)
SB  - IM
MH  - Animals
MH  - Biomarkers/blood/metabolism
MH  - Carcinogens/toxicity
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Cell Shape/drug effects
MH  - Cells, Cultured
MH  - Chemical and Drug Induced Liver Injury/*metabolism/pathology/physiopathology
MH  - *Disease Models, Animal
MH  - Disease Progression
MH  - Female
MH  - Liver/*drug effects/metabolism/pathology/physiopathology
MH  - Liver Neoplasms/etiology
MH  - Liver X Receptors/*agonists/antagonists & inhibitors/genetics/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oxysterols/metabolism/*pharmacology
MH  - Pluripotent Stem Cells/cytology/drug effects/metabolism/pathology
MH  - Pyridines/toxicity
MH  - RNA Interference
MH  - Sulfotransferases/antagonists & inhibitors/chemistry/genetics/*metabolism
OTO - NOTNLM
OT  - Hepatic oval cells
OT  - Hydroxysteroid sulfotransferase 2B1
OT  - LXR
OT  - Oxysterol
OT  - Proliferation
EDAT- 2016/04/08 06:00
MHDA- 2017/03/08 06:00
CRDT- 2016/04/08 06:00
PHST- 2015/11/05 00:00 [received]
PHST- 2016/03/21 00:00 [accepted]
PHST- 2016/04/08 06:00 [pubmed]
PHST- 2017/03/08 06:00 [medline]
PHST- 2016/04/08 06:00 [entrez]
AID - 10.1007/s00204-016-1693-z [pii]
AID - 10.1007/s00204-016-1693-z [doi]
PST - ppublish
SO  - Arch Toxicol. 2017 Jan;91(1):271-287. doi: 10.1007/s00204-016-1693-z. Epub 2016 
      Apr 6.