Senescent fibroblasts regulate skin pigmentation
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Tae Jun Park | - |
dc.contributor.author | 윤정은 | - |
dc.date.accessioned | 2019-04-01T16:41:00Z | - |
dc.date.available | 2019-04-01T16:41:00Z | - |
dc.date.issued | 2019-02 | - |
dc.identifier.other | 28508 | - |
dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/14987 | - |
dc.description | 학위논문(석사)--아주대학교 일반대학원 :의생명과학과,2019. 2 | - |
dc.description.abstract | 피부 노화는 색소분비체계가 변형된 중요한 외부 과정이다. 그러한 이유로 근본적인 노화 기전을 노화 색소 침착에서 노화된 세포의 역할을 조사하였다. 방법 : 노인성 흑색종과 그 주변피부에서 얻은 생검에서 세포노화 표지자인 p16INK4A에 대하여 분석하였다. 노화된 섬유 아세포에서 분비되는 표현형을 밝히기 위하여 노인성 흑색종과 노화된 섬유 아세포에서 마이크로 어레이, RNA 시퀀싱, 그리고 메틸화 어레이 분석을 진행하였다. 결과 : In vivo 상에서 노화와 연관된 부위에 노화된 섬유아세포가 축적되어 있었다. 세포의 표현형 변환으로 프로모터 메틸화에 의한 SDF1의 감소가 나타났다. 이에 따라 간질- 상피 상호작용을 통하여 멜라닌 세포의 분화가 유도되었고, 궁극적으로 피부 색소 침착을 유도했다. 결론 : 노화된 피부는 노화 된 섬유 아세포의 비율이 증가하여있다. 표현형 변환을 가진 세포는 SDF1의 발현이 감소되어 있었으며, 이는 멜라닌 생성과정에 작용하여 색소 침착을 감소시킨다. 이 자료는 색소 침착에 대하여 간질 표적치료와 같은 새로운 치료적 패러다임을 제시한다. | - |
dc.description.tableofcontents | I. INTRODUCTION 1 II. MATERIALS AND METHODS 2 1. Cell culture 2 2. Enzyme-linked immunosorbent assay (ELISA) 2 3. Institutional review board statement 3 4. RNA sequencing 3 5. Senescence Associated β-Galactosidase (SA-β-Gal) Staining 3 6. Sequencing analysis of bisulfite-treated DNA 3 7. In vitro model of senescent fibroblasts 4 8. Promoter analysis 4 9. Ex vivo skin organ culture and pigmentation assays in cultured skin 5 10. Melanin contents and tyrosinase activity assay 5 11. Lentivirus production 6 12. Real-time PCR analysis 6 13. Western blot analysis 7 14. Immunocytochemistry and immunohistochemical analysis 7 15. Microscope image acquisition 8 16. Statistical analysis 8 III. RESULT 9 1. Senescent fibroblasts in senile lentigo 9 2. Senescent fibroblasts promote skin pigmentation 14 3. SDF1 level was downregulated in senescent fibroblasts and senile lentigo 19 4. Senescent fibroblasts involve SDF1 deficiency under promoter methylation 25 5. SDF1 and CXCR4 expression in skin cells 31 6. Effects of SDF1 in skin pigmentation 34 7. CXCR4 inhibition by AMD3100 increased melanin synthesis 29 8. Effects of SDF1 in skin pigmentation 39 IV. DISCUSSION 42 V. REFERENCES 46 국문요약 50 | - |
dc.language.iso | kor | - |
dc.publisher | The Graduate School, Ajou University | - |
dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
dc.title | Senescent fibroblasts regulate skin pigmentation | - |
dc.title.alternative | Yoon Jungeun | - |
dc.type | Thesis | - |
dc.contributor.affiliation | 아주대학교 일반대학원 | - |
dc.contributor.alternativeName | Yoon Jungeun | - |
dc.contributor.department | 일반대학원 의생명과학과 | - |
dc.date.awarded | 2019. 2 | - |
dc.description.degree | Master | - |
dc.identifier.localId | 905301 | - |
dc.identifier.uci | I804:41038-000000028508 | - |
dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/common/orgView/000000028508 | - |
dc.description.alternativeAbstract | Cutaneous ageing is an important extrinsic process that modifies the pigmentary system. Because cellular senescence is a fundamental ageing mechanism, we examined the role of senescent cells in ageing pigmentation. Methods: Biopsies obtained from senile lentigo and perilesional normal skin were assayed for a marker of cellular senescence, p16INK4A. To determine the secretory phenotypes of senescent fibroblasts, we performed microarray, RNA sequencing and methylation array analyses in senile lentigo and senescent fibroblasts. Results: In vivo, senescent fibroblasts accumulated at the sites of age-related pigmentation. Phenotype switching of the cells resulted in the repression of stromal-derived factor 1 (SDF1) by promoter methylation. SDF1 induced melanocyte differentiation via stromal-epithelial interactions, ultimately driving skin pigmentation. Furthermore, the elimination of senescent fibroblasts from pigmented skin using radiofrequency was accompanied by skin lightening, rendering it a potential target for treatment. Conclusion: Aged pigmented skin contains an increasing proportion of senescent fibroblasts. Cells with phenotype switching exhibited a loss of SDF1, which stimulates the melanogenic process and thereby contributes to ageing pigmentation. These data may promote the development of new therapeutic paradigms, such as a stroma-targeting therapy for pigmentary disorders. | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.