Deficiency of BPOZ2 Decreases Liver Fibrosis After Chronic Carbon Tetrachloride Administration in Mice

Feng Zhang; Suying Dang; Runzhe Shu; Yougui Xiang; Ying Kuang; Jian Fei; Zhugang Wang

doi:10.1177/1091581814566472

Deficiency of BPOZ2 Decreases Liver Fibrosis After Chronic Carbon Tetrachloride Administration in Mice

Int J Toxicol. 2015 Mar-Apr;34(2):204-10. doi: 10.1177/1091581814566472. Epub 2015 Jan 7.

Authors

Feng Zhang¹, Suying Dang², Runzhe Shu³, Yougui Xiang⁴, Ying Kuang⁵, Jian Fei⁵, Zhugang Wang⁶

Affiliations

¹ Department of Clinical Laboratory, Quzhou People's Hospital, Quzhou, Zhejiang, China State Key Laboratory of Medical Genomics, Research Centre for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Model Organism Division, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai, China suyingdang@shsmu.edu.cn.
³ State Key Laboratory of Medical Genomics, Research Centre for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Model Organism Division, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Research Center for Model Organisms, Shanghai, China.
⁵ Shanghai Research Center for Model Organisms, Shanghai, China.
⁶ State Key Laboratory of Medical Genomics, Research Centre for Experimental Medicine of Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China Model Organism Division, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Research Center for Model Organisms, Shanghai, China zhugangw@shsmu.edu.cn.

PMID: 25568138
DOI: 10.1177/1091581814566472

Abstract

Bood POZ containing gene type 2 (BPOZ2), a Broad-Complex, Tramtrack, and Bric a brac domain containing protein, is an adaptor protein for the E3 ubiquitin ligase scaffold protein CUL3. It plays an important role in acute carbon tetrachloride (CCl4)-induced liver injury and regeneration in mice. In this study, we investigated the role of BPOZ2 in the process of liver fibrosis induced by chronic CCl4 treatment. The results indicate that BPOZ2 deficiency decreases sustained activation of hepatic stellate cells, attenuates collagen αI(I) and tissue inhibitor of matrix metalloprotease 1 expression, and decreases liver fibrosis after repeated CCl4 administration. These findings suggest BPOZ2 as a new therapeutic target for the prevention and treatment of hepatic fibrosis in chronic liver disease.

Keywords: BPOZ2; HSC; TIMP-1; carbon tetrachloride; liver fibrosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Carbon Tetrachloride / toxicity*
Collagen / analysis
Female
Liver / chemistry
Liver / drug effects
Liver / pathology
Liver Cirrhosis / chemically induced*
Liver Cirrhosis / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Nuclear Proteins / deficiency*
Nuclear Proteins / physiology
Reverse Transcriptase Polymerase Chain Reaction

Substances

Abtb2 protein, mouse
Nuclear Proteins
Collagen
Carbon Tetrachloride