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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress

  • Kim, Hyeon Ju (Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine) ;
  • Lee, Yoseob (Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine) ;
  • Fang, Sungsoon (Brain Korea 21 PLUS Project for Medical Science, Yonsei University) ;
  • Kim, Won (Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center) ;
  • Kim, Hyo Jung (Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine) ;
  • Kim, Jae-woo (Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine)
  • Received : 2019.11.11
  • Accepted : 2019.12.02
  • Published : 2020.06.30
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASH-fibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor-β (TGF-β) and free fatty acids (FFA)-treated LX-2 cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis. Consistently, GPx7 overexpression in LX-2 cells led to the suppression of ROS production and reduced the expression of pro-fibrotic and pro-inflammatory genes. Further, NASH fibrosis induced by choline-deficient amino acid defined, high fat diet (CDAHFD) feeding was significantly accelerated by knockdown of GPx7, as evidenced by up-regulated liver fibrosis and inflammation compared with CDAHFD control mice. Collectively, these results suggest that GPx7 might be a novel therapeutic target to prevent the progression and development of NAFLD.

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References

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