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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 장선영 | - |
| dc.contributor.author | 곽민규 | - |
| dc.date.issued | 2021-08 | - |
| dc.identifier.other | 31074 | - |
| dc.identifier.uri | https://aurora.ajou.ac.kr/handle/2018.oak/20405 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :약학과,2021. 8 | - |
| dc.description.tableofcontents | ⅠIntroduction 1 ⅡMaterials and methods 4 1. Mice 4 2. RNA extraction 4 a. Organoid 4 b. In vivo 5 3. Real Time-PCR 5 4. Endotoxin analysis 6 5. Immuno-fluorescence (IF) staining 7 6. Organoid size and budding measurements 7 7. Organoid culture 7 8. HIF stabilizer 8 9. Statics 8 Ⅲ Results 11 A. The role of HIF stabilization on the gut organoid 11 B. HIF Stabilization promotes cell growth in organoid 13 C. HIF unaffected gut barrier at steady-state small intestine 15 D. HIF unaffected gut barrier at steady-state gut permeability 17 E. The role of AhR on gut barrier 19 F. AhR deficiency promotes cell growth 21 G. AhR deficiency promotes IECs proliferation and induces an increase in gut permeability 23 H. AhR deficiency leads to an increase in gut permeability 25 I. The role of HIF in AHR deficiency on the gut barrier 27 J. HIF did not increase uncontrolled cell proliferation caused by AhR deficiency 29 K. HIF restore the increased gut permeability caused by AhR deficiency 31 L. HIF inhibits the increase gut permeability caused by AhR deficiency in vivo 33 Ⅳ Discussion 35 ⅤConclusion 37 Reference 38 국문초록 40 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Effect of complementary relationship between hypoxia-inducible factor-1 and aryl hydrocarbon receptor on intestinal barrier | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 약학과 | - |
| dc.date.awarded | 2021. 8 | - |
| dc.description.degree | Master | - |
| dc.identifier.uci | I804:41038-000000031074 | - |
| dc.identifier.url | https://dcoll.ajou.ac.kr/dcollection/common/orgView/000000031074 | - |
| dc.subject.keyword | Aryl hydrocarbon receptors | - |
| dc.subject.keyword | Gut barrier | - |
| dc.subject.keyword | Hypoxia-inducible factor-1 | - |
| dc.subject.keyword | Inflammatory bowel disease | - |
| dc.description.alternativeAbstract | The exact cause of inflammatory bowel disease is unknown, and the breakdown of the intestinal barrier causes the leaky gut syndrome. Hypoxia-inducing factors (HIF) and aryl hydrocarbon receptors (AhR) are known to be important factors in maintaining intestinal barrier homeostasis. Organoids and animal models were used to study the effects of HIF and AhR on the intestinal barrier. Stabilizing of HIF increased cell proliferation and increased junctional molecule expression. Organoid size and budding were increased. Barrier integrity in mice was no change after stabilizing of HIF. AhR deficient organoid was generated from the small intestine of AhR deficient mice. Depletion of aryl hydrocarbon receptors resulted in increased cell proliferation and altered intestinal permeability. Immunofluorescence staining showed increased size and budding. AhR deficient intestine had increased permeability, serum endotoxin, and bacterial translocation compared with wild type intestine. Stabilization of HIF in AhR deficient organoids restored intestinal permeability. AhR deficient mice treated with HIF stabilizer decreased endotoxin concentrations and bacterial translocation. Therefore, the increased intestinal permeability due to AhR deficiency can be restored by stabilization of HIF. This has the potential to contribute to the treatment of patients with inflammatory bowel disease and colorectal cancer. | - |
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