title: Cystathionine γ-Lyase Deficiency Exacerbates CCl4-Induced Acute Hepatitis and Fibrosis in the Mouse Liver.
abstract: OBJECTIVE
  The present study examined the role of cystathionine γ-lyase (CSE) in carbon tetrachloride (CCl4)-induced liver damage.
  
  
  RESULTS
  A CSE gene knock-out and luciferase gene knock-in (KI) mouse model was constructed to study the function of CSE and to trace its expression in living status. CCl4or lipopolysaccharide markedly downregulated CSE expression in the liver of mice. CSE-deficient mice showed increased serum alanine aminotransferase and aspartate aminotransferase levels, and liver damage after CCl4challenge, whereas albumin and endogenous hydrogen sulfide (H2S) levels decreased significantly. CSE knockout mice showed increased serum homocysteine levels, upregulation of inflammatory cytokines, and increased autophagy and IκB-α degradation in the liver in response to CCl4treatment. The increase in pro-inflammatory cytokines, including tumor necrosis factor-alpha in CSE-deficient mice after CCl4challenge, was accompanied by a significant increase in liver tissue hydroxyproline and α-smooth muscle actin and histopathologic changes in the liver. However, H2S donor pretreatment effectively attenuated most of these imbalances.
  
  
  METHODS
  Here, a CSE knock-out and luciferase KI mouse model was established for the first time to study the transcriptional regulation of CSE expression in real time in a non-invasive manner, providing information on the effects and potential mechanisms of CSE on CCl4-induced liver injury.
  
  
  CONCLUSIONS
  CSE deficiency increases pro-inflammatory cytokines in the liver and exacerbates acute hepatitis and liver fibrosis by reducing H2S production from L-cysteine in the liver. The present data suggest the potential of an H2S donor for the treatment of liver diseases such as toxic hepatitis and fibrosis. Antioxid. Redox Signal. 27, 133-149.
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .
authors.forename: Lei
authors.initials: L
authors.lastname: Ci
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .
authors.forename: Xingyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Gu
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .|2 Shanghai Research Center for Model Organisms , Shanghai, China .
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .
authors.forename: Ziping
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .
authors.forename: Mengjie
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .
authors.forename: Jiahao
authors.initials: J
authors.lastname: Shi
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: 2 Shanghai Research Center for Model Organisms , Shanghai, China .
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 1 School of Life Science and Techonology, Tongji University , Shanghai, China .|2 Shanghai Research Center for Model Organisms , Shanghai, China .
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000172:deficiency* / Q000235:genetics; D003545:Cysteine / Q000378:metabolism; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D055786:Gene Knockout Techniques; D006862:Hydrogen Sulfide / Q000378:metabolism; D008297:Male; D051379:Mice
chemical_list: D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003542:Cystathionine gamma-Lyase; D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: carbon tetrachloride; hepatitis; hydrogen sulfide; liver fibrosis