Retinol dehydrogenase 13 deficiency diminishes carbon tetrachloride-induced liver fibrosis in mice

Xiaofang Cui; Suying Dang; Yan Wang; Yan Chen; Jia Zhou; Chunling Shen; Ying Kuang; Jian Fei; Lungen Lu; Zhugang Wang

doi:10.1016/j.toxlet.2016.11.010

Retinol dehydrogenase 13 deficiency diminishes carbon tetrachloride-induced liver fibrosis in mice

Toxicol Lett. 2017 Jan 4:265:17-22. doi: 10.1016/j.toxlet.2016.11.010. Epub 2016 Nov 16.

Authors

Xiaofang Cui¹, Suying Dang², Yan Wang³, Yan Chen⁴, Jia Zhou⁴, Chunling Shen², Ying Kuang⁵, Jian Fei⁵, Lungen Lu³, Zhugang Wang⁶

Affiliations

¹ State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200025, China; Model Organism Division, E-Institutes of Shanghai Jiao Tong Universities School of Medicine (SJTUSM), Shanghai, 200025, China; Shanghai Research Center for Model Organisms, Shanghai, 201203, China.
² State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200025, China; Shanghai Research Center for Model Organisms, Shanghai, 201203, China.
³ Department of Gastroenterology, Shanghai First People's Hospital Affiliated to SJTUSM, Shanghai, 200080, China.
⁴ State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200025, China.
⁵ Shanghai Research Center for Model Organisms, Shanghai, 201203, China.
⁶ State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Shanghai Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200025, China; Model Organism Division, E-Institutes of Shanghai Jiao Tong Universities School of Medicine (SJTUSM), Shanghai, 200025, China; Shanghai Research Center for Model Organisms, Shanghai, 201203, China. Electronic address: zhugangw@shsmu.edu.cn.

PMID: 27865848
DOI: 10.1016/j.toxlet.2016.11.010

Abstract

Retinol dehydrogenase 13 (RDH13) is a mitochondrion-localized member of the short-chain dehydrogenases/reductases (SDRs) superfamily that participates in metabolism of some compounds. Rdh13 mRNA is most highly expressed in mouse liver. Rdh13 deficiency reduces the extent of liver injury and fibrosis, reduces hepatic stellate cell (HSC) activation, attenuates collagen I (II), tissue inhibitor of metalloproteinase 1 (TIMP-1) and transforming growth factor beta 1 (Tgf-β1) expression. The results indicate an important role of Rdh13 and suggest RDH13 as a possible new therapeutic target for CCl₄-induced fibrosis.

Keywords: Carbon tetrachloride; Hepatic stellate cells; Knockout; Liver fibrosis; Retinol dehydrogenase 13.

MeSH terms

Alcohol Oxidoreductases / deficiency*
Alcohol Oxidoreductases / genetics
Animals
Blotting, Western
Carbon Tetrachloride / toxicity*
Chemical and Drug Induced Liver Injury / enzymology*
Chemical and Drug Induced Liver Injury / metabolism
Chemical and Drug Induced Liver Injury / pathology
Collagen / biosynthesis
Female
Hepatic Stellate Cells / enzymology
Hepatic Stellate Cells / pathology
Immunohistochemistry
Liver Cirrhosis / enzymology*
Liver Cirrhosis / metabolism
Liver Cirrhosis / pathology
Male
Mice, Inbred C57BL
Mice, Knockout
Real-Time Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-1 / genetics
Transforming Growth Factor beta1 / genetics

Substances

Timp1 protein, mouse
Tissue Inhibitor of Metalloproteinase-1
Transforming Growth Factor beta1
Collagen
Carbon Tetrachloride
Alcohol Oxidoreductases
retinol dehydrogenase 13, mouse