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Functional analysis of GPx7 in non-alcoholic fatty liver disease

Other Titles
 비 알코올성 지방간질환에서의 GPx7의 기능분석 
Authors
 김현주 
College
 College of Medicine (의과대학) 
Department
 Department of Medical Science 
Degree
석사
Issue Date
2020
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. NAFLD can progress to further irreversible liver failure such as non-alcoholic steatohepatitis (NASH) and cirrhosis. However, the molecular mechanisms involved in disease progression from simple steatosis to fibrosis remain poorly understood. This study aims to elucidate the molecular mechanisms that regulate the progression of NAFLD. In this study, I analyzed RNA sequencing (RNA-seq) data to profile gene expression in simple steatosis and NASH-fibrosis model; cellular model (1) oleic acid (OA)-treated Hepa1-6 cells (murine hepatoma cell line), (2) transforming growth factor-β (TGF-β)-treated LX-2 cells (human stellate cell line) and mice model (3) simple steatosis of high-fat-diet (HFD)-fed mice liver (4) NASH-fibrosis of choline-deficient, L-amino acid-defined, high-fat-diet (CDAHFD)-fed mice liver. As a result of RNA-seq analysis, I found that glutathione peroxidase 7 (GPx7) expression was significantly increased in NASH-fibrosis compare to normal liver. So, I examined the role of GPx7 in cells. As a results, knockdown of the GPx7 expression using siRNA increased liver fibrosis and inflammation, whereas overexpression of GPx7 suppressed liver fibrosis and inflammation related gene expression in LX-2 cells. To determine whether GPx7 play a role in vivo, mice are fed CDAHFD for three weeks and a week before the sacrifice injected adenovirus containing short hairpin RNA (Ad-shRNA). As expected, knockdown of GPx7 induced liver fibrosis and inflammation as shown by masson’s trichrome staining and plasma ALT and AST level, respectively. These results suggest that GPx7 may be a novel regulator of liver fibrosis. Oxidative stress has been implicated in the pathogenesis of NAFLD. To determine whether GPx7 is involved in oxidative stress regulation, I measured reactive oxygen species (ROS) production in GPx7 overexpressed LX-2 cells. As showing that overexpression of GPx7 reduced oxidative stress, thereby attenuated NASH. Taken together, these results indicate that GPx7 can alleviate oxidative stress and prevent liver fibrosis, suggesting that activating GPx7 enzyme activity is a useful therapeutic strategy for NASH-fibrosis.
Files in This Item:
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Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 2. Thesis
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181137
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