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Coumestrol, a component of soybean sprout, attenuates UVB-induced skin photoaging by targeting FLT3 : 자외선에 의한 FLT3 활성 저해를 통한 쿠메스트롤의 피부노화 개선효능 및 작용기작 규명
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 이기원 | - |
dc.contributor.author | 박가은 | - |
dc.date.accessioned | 2017-07-14T06:43:21Z | - |
dc.date.available | 2017-07-14T06:43:21Z | - |
dc.date.issued | 2014-08 | - |
dc.identifier.other | 000000022167 | - |
dc.identifier.uri | https://hdl.handle.net/10371/125882 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2014. 8. 이기원. | - |
dc.description.abstract | Skin aging is a naturally occurring process by senescence. However, exposure to ultraviolet (UV) light triggers wrinkle formation and sagging of skin due to collagen degradation by activating matrix metalloproteinases (MMPs). In this study, I show that coumestrol, a metabolite of soybean isoflavone daidzein, has stronger preventive effect on skin photoaging than daidzin and daidzein in three-dimensional human skin equivalent model. The results showed that coumestrol inhibits UVB-induced MMP-1 activity and MMP-1 expression. To identify a direct molecular target of coumestrol, whole human kinase profiling assay was conducted and FLT3 kinase was proposed as a novel target protein of coumestrol in UVB-induced signaling pathway in skin. Coumestrol suppresses FLT3 kinase activity, and subsequently, Ras/MEK/ERK and Akt/p70S6K pathway. This led to the suppressed AP-1 activity and in turn, diminished MMP-1 gene transcription by coumestrol. 4-APIA, pharmacological inhibitor of FLT3, inhibited MMP-1 expression and induced similar signal transduction changes with coumestrol. Taken together, coumestrol inhibits UVB-induced MMP-1 expression by suppressing FLT3 kinase activity. This finding suggests that coumestrol is a novel dietary compound with potential utilization in preventing and improving UVB-associated skin aging. | - |
dc.description.tableofcontents | Abstract ............................................................................................ i
Contents .......................................................................................... iii Ⅰ. Introduction ................................................................................ 1 Ⅱ. Materials and methods ................................................................ 4 2.1. Chemicals and reagents ......................................................... 4 2.2. Cell culture and UVB irradiation .......................................... 5 2.3. Three dimensional human skin equivalent ............................ 5 2.4. Cell viability .......................................................................... 6 2.5. Histological examination ....................................................... 6 2.6. Immunohistochemical staining .............................................. 7 2.7. Enzyme-linked immunosorbent assay ................................... 8 2.8. MMP-1 activity assay ............................................................ 8 2.9. Real-time reverse transcriptase PCR ..................................... 9 2.10. AP-1 reporter gene assay ................................................... 10 2.11. Western blot analysis .......................................................... 11 2.12. Zymography ...................................................................... 12 2.13. Kinase profiling analysis and kinase assay ........................ 12 2.14. Statistical analysis ............................................................. 13 Ⅲ. Result ........................................................................................ 14 3.1. Coumestrol inhibits UVB-induced collagen degradation and collagenase expression in three dimensional human skin equivalent ........................................................................... 14 3.2. Coumestrol suppresses UVB-induced MMP-1 activity by modulating MMP-1 expression .......................................... 18 3.3. Coumestrol reduces the FLT3 kinase activity ..................... 21 3.4. Coumestrol decreases mRNA of MMP-1 transcription via modulating Raf/MEK/ERK and Akt/p70S6K signal transductions …………………………………………....... 30 3.5. 4-APIA, Pharmacological inhibitor of FLT3, inhibits UVB-induced MMP-1 expression …………...….………………. 33 Ⅳ. Discussion ................................................................................ 36 Ⅴ. References ................................................................................ 42 Ⅵ. 국문초록 ............................................................................... 50 Ⅶ. 감사의 글 ............................................................................. 52 | - |
dc.format | application/pdf | - |
dc.format.extent | 943191 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Coumestrol | - |
dc.subject | FLT3 | - |
dc.subject | MMP-1 | - |
dc.subject | UVB | - |
dc.subject.ddc | 630 | - |
dc.title | Coumestrol, a component of soybean sprout, attenuates UVB-induced skin photoaging by targeting FLT3 | - |
dc.title.alternative | 자외선에 의한 FLT3 활성 저해를 통한 쿠메스트롤의 피부노화 개선효능 및 작용기작 규명 | - |
dc.type | Thesis | - |
dc.description.degree | Master | - |
dc.citation.pages | 53 | - |
dc.contributor.affiliation | 농업생명과학대학 농생명공학부 | - |
dc.date.awarded | 2014-08 | - |
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