Archives of Toxicology

, Volume 91, Issue 1, pp 271–287 | Cite as

Upregulation of hydroxysteroid sulfotransferase 2B1b promotes hepatic oval cell proliferation by modulating oxysterol-induced LXR activation in a mouse model of liver injury

  • Zhengyang Wang
  • Xiaoming Yang
  • Liang Chen
  • Xiuling Zhi
  • Hanyu Lu
  • Yanxia Ning
  • Joe Yeong
  • Sifeng Chen
  • Lianhua Yin
  • Xinhong WangEmail author
  • Xiaobo LiEmail author
Molecular Toxicology


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.


Hydroxysteroid sulfotransferase 2B1 Hepatic oval cells Oxysterol LXR Proliferation 









ATP-binding cassette transporters G5 and G8




Carbon tetrachloride


Choline-deficient ethionine-supplemented diet


Cytokine-inducible SH2-containing protein


Cytokeratin 19


Myelocytomatosis oncogene




Epithelial cell adhesion molecule


Glycoprotein 130


Interleukin 6


Liquid chromatography and mass spectrometry


Liver X receptor


Partial hepatectomy


Proliferating cell nuclear antigen


Mitogen-activated protein kinase-2


Quantitative real-time polymerase chain reaction


Suppressor of cytokine signaling 3


Signal transducer and activator of transcription 3


Hydroxysteroid sulfotransferase 2B1









We thank Dr. Shunlin Ren for generously providing SULT2B1 adenovirus vectors (Ad-SULT2B1). We further thank Dr. Chih-hao Lee for providing expression vector for Gal4-DNA binding domain (DBD)-LXRα ligand binding domain (LBD) fusion protein and Gal4 luciferase reporter vector. This work was supported by the National Natural Science Foundation of China (NSFC 81270497, NSFC 81572713), Shanghai Municipal Natural Science Foundation (12ZR1403000), and Natural Science Foundation of Ningxia Province of China (NX14074). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Ethical approval

All procedures were in accordance with the ethical standards of the institution.

Conflict of interest

The authors have no competing interests to disclose.

Supplementary material

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Supplementary material 1 (TIFF 542 kb)
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Supplementary material 2 (TIFF 146 kb)
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Supplementary material 3 (TIFF 656 kb)
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Supplementary material 4 (TIFF 946 kb)
204_2016_1693_MOESM5_ESM.docx (20 kb)
Supplementary material 5 (DOCX 20 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Zhengyang Wang
    • 1
  • Xiaoming Yang
    • 2
  • Liang Chen
    • 1
  • Xiuling Zhi
    • 1
  • Hanyu Lu
    • 1
  • Yanxia Ning
    • 1
  • Joe Yeong
    • 3
    • 4
  • Sifeng Chen
    • 1
  • Lianhua Yin
    • 1
  • Xinhong Wang
    • 1
    Email author
  • Xiaobo Li
    • 1
    Email author
  1. 1.Department of Physiology and Pathophysiology, School of Basic Medical SciencesFudan UniversityShanghaiChina
  2. 2.Ningxia Medical UniversityYinchuanChina
  3. 3.Department of PathologySingapore General HospitalSingaporeSingapore
  4. 4.Agency for Science, Technology and Research (A∗STAR)Singapore Immunology Network (SIgN)SingaporeSingapore

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