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Study on the role of RIPK3 in lymphomagenesis and hepatic steatosis
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | 하, 유진 | - |
| dc.date.accessioned | 2023-11-16T05:43:57Z | - |
| dc.date.available | 2023-11-16T05:43:57Z | - |
| dc.date.issued | 2023 | - |
| dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/26850 | - |
| dc.language.iso | en | - |
| dc.title | Study on the role of RIPK3 in lymphomagenesis and hepatic steatosis | - |
| dc.type | Thesis | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000032999 | - |
| dc.subject.keyword | RIPK3 | - |
| dc.subject.keyword | T cell | - |
| dc.subject.keyword | Lymphoma | - |
| dc.subject.keyword | NAFLD | - |
| dc.subject.keyword | Hepatic steatosis | - |
| dc.description.degree | Doctor | - |
| dc.contributor.department | 대학원 의생명과학과 | - |
| dc.contributor.affiliatedAuthor | 하, 유진 | - |
| dc.date.awarded | 2023 | - |
| dc.type.local | Theses | - |
| dc.citation.date | 2023 | - |
| dc.embargo.liftdate | 9999-12-31 | - |
| dc.embargo.terms | 9999-12-31 | - |
| dc.description.tableOfContents | I. INTRODUCTION 1
A. Necroptosis 1 B. Roles of RIPK3 2 C. Necroptosis in human pathogenesis 3 D. T cell homeostasis in thymus 4 E. Non-alcoholic fatty liver disease (NAFLD) 5 F. The aim of this study 6 II. MATERIALS AND METHODS 7 A. Mice 7 B. Adeno associated virus (AAV)-mediated RIPK3 overexpression 8 C. Cell culture 9 D. Flow cytometric analysis 9 E. Serum biochemistry 10 F. Liver triglyceride measurement 11 G. Histological analysis 11 H. Proximal ligation assay (PLA) 13 I. Western Blot 13 J. Immunoprecipitation 14 K. Tandem Affinity Purification and Mass Spectrometry (TAP-MS) analysis 15 L. In vitro kinase assay 15 M. RNA-seq analysis 16 N. RNA extraction, cDNA synthesis and quantitative RT-PCR 16 O. Statistical analysis 17 III. RESULTS 19 Part I . RIPK3 maintains the homeostatic proliferation of CD4+CD8+ double-positive (DP) T cells to restrain early onset of thymic lymphoma 19 A. RIPK3 deficiency leads to hyperproliferation of DP T cells in the thymus. 19 B. Increased DP T cells are independent of RIPK3-MLKL necroptosis pathway. 26 C. RIPK3 deficiency accelerates tumor progression in a carcinogen-induced mouse model. 29 D. RIPK3 deficiency potentiates thymic lymphoma progression in p53-/- mice. 33 E. RIPK3 deficiency enhances thymic lymphoma via TCR-dependent ERK hyperactivation. 38 F. LCK interacts with RIPK3 and phosphorylates its tyrosine residue. 40 G. RIPK3 negatively regulates ERK phosphorylation through potentiation of PP2A activity. 45 H. Pharmacological modulation of PP2A activity regulates DP thymocyte proliferation in a carcinogen-induced mouse model. 48 Part II . RIPK3 protects aberrant hepatic fat accumulation via regulation of hepatic lipid metabolism. 54 A. RIPK3 deficiency leads to age-dependent aberrant hepatic fat accumulation. 54 B. RIPK3 was not the causative factor for hepatic steatosis 61 C. Liver-specific overexpression of RIPK3 attenuates HFD-induced hepatic steatosis. 68 D. RIPK3 gene signatures were correlated with lipid metabolism. 77 IV. DISCUSSION 80 Part I . RIPK3 maintains the homeostatic proliferation of CD4+CD8+ double-positive (DP) T cells to restrain early onset of thymic lymphoma 80 Part II . RIPK3 protects aberrant hepatic fat accumulation via regulation of hepatic lipid metabolism. 83 V. REFERENCES 85 | - |
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