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Role of visfatin in pathogenesis and progression of non-alcoholic fatty liver disease
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | 허, 유정 | - |
| dc.date.accessioned | 2021-11-10T05:51:56Z | - |
| dc.date.available | 2021-11-10T05:51:56Z | - |
| dc.date.issued | 2021 | - |
| dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/19775 | - |
| dc.description.abstract | 비공개 | - |
| dc.description.tableofcontents | Ⅰ. Introduction 1
A. Progression of Non-alcoholic fatty liver disease (NAFLD) 1 B. Insulin resistance 2 C. Visfatin 2 D. Hepatic inflammation 3 E. Hepatic fibrosis 6 F. Aims of the study 7 Ⅱ. Materials and methods 8 A. Reagents 8 B. HepG2 cell culture 8 C. THP-1 and LX-2 cell culture 8 D. Immunoblotting 9 E. Reverse transcriptase-polymerase chain reaction (RT-PCR) 10 F. Flow cytometric measurement of reactive oxygen species (ROS) 10 G. Immunocytochemistry 11 H. Human cytokine array and image analyses 11 I. Enzyme-linked immunosorbent assay (ELISA) 11 J. Animal studies 12 1. High fat (HF) diet model 12 2. Methionine/Choline Deficient (MCD) diet model 12 K. Isolation and treatment of liver cells 13 L. ROS/RNS assay 13 M. Histopathological analyses 13 N. Statistical analyses 13 Ⅲ. Results 21 PART A. Visfatin induces insulin resistance and inflammation via the NF-κB and STAT3 signaling pathway in hepatocytes 21 1. Effect of visfatin on the expression of lipid metabolism-related genes in HepG2 cells 21 2. Visfatin enhanced ER stress and ROS production in HepG2 cells 23 3. Visfatin induced insulin resistance in a dose-dependent manner in HepG2 cells 26 4. Visfatin induced the production of pro-inflammatory cytokines in HepG2 cells 28 5. Visfatin activated NF-κB/STAT3 signaling and expression of IRS-1 S 307 in HepG2 cells 30 6. JAK/STAT3 and NF-κB inhibitors inhibited visfatin-induced expression of inflammatory cytokines and insulin resistance in HepG2 cells 34 PART B. Visfatin induced the expression of CCL20 in macrophages via the NF-κB and MKK3/6-p38 signaling pathway and activated hepatic stellate cells (HSCs) 37 1. Visfatin treatment promoted differentiation of THP-1 cells to M1 macrophages 37 2. Visfatin upregulated the expression of CCL20 in THP-1 cells 39 3. Visfatin activated NF-κB and MAPK cascade pathways in THP-1 cells 41 4. Inhibition of NF-κB and MAPK cascade pathways attenuated visfatin-induced expression of CCL20 and fibrosis markers in HSCs 44 5. Visfatin-induced CCL20 enhanced the expression of fibrosis genes in LX-2 cells 46 6. Visfatin enhanced the expression of fibrosis markers in LX-2 cells 49 PART C. Visfatin exacerbates hepatic inflammation and fibrosis in an animal model of NAFLD 51 1. Increased hepatic expression of visfatin was associated with hepatic inflammation 51 2. Visfatin induced marked steatosis and liver inflammation in mice on high fat diet (HFD) 54 3. Visfatin aggravated hepatic steatosis and inflammation in the liver of MCD-diet fed mice 56 4. Visfatin induced infiltration of immune cells and production of chemokines in the liver 58 5. Visfatin induced the expression and production of chemokines in the liver 60 6. Visfatin induced ER stress and ROS generation 62 7. Visfatin accelerated the development of liver fibrosis in MCD-diet-fed mice. 64 Ⅳ. Discussion 66 Ⅴ. Conclusion 74 REFERENCES 75 국문요약 87 | - |
| dc.language.iso | en | - |
| dc.title | Role of visfatin in pathogenesis and progression of non-alcoholic fatty liver disease | - |
| dc.type | Thesis | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000030491 | - |
| dc.description.degree | Doctor | - |
| dc.contributor.department | 대학원 의생명과학과 | - |
| dc.contributor.affiliatedAuthor | 허, 유정 | - |
| dc.date.awarded | 2021 | - |
| dc.type.local | Theses | - |
| dc.citation.date | 2021 | - |
| dc.embargo.liftdate | 9999-12-31 | - |
| dc.embargo.terms | 9999-12-31 | - |
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