Clusterin이 TGF-β 신호전달 기전을 통해 색소형성과정에 미치는 영향
- 주제(키워드) Melanogenesis , Melanocyte , Clusterin , Fibroblast-derived factor , TGF-β
- 발행기관 아주대학교
- 지도교수 강희영
- 발행년도 2017
- 학위수여년월 2017. 2
- 학위명 석사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000024092
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Clusterin has been known as a biomarker of aging and is highly induced in stressed and senescent cells. In this study, RNA sequencing analysis showed transcripts for clusterin were highly expressed in UV irradiated fibroblasts. A considerable increase of clusterin was detected in the culture medium. We found that the clusterin associates with solar elastosis and is overexpressed in the acutely UV-irradiated skin. To investigate the effect of clusterin on melanogenesis, normal human melanocytes were treated with conditioned media of fibroblasts infected with clusterin-lentivirus or sh-clusterin. It was found that clusterin inhibits melanogenesis through MITF/tyrosinase downregulation via TGF-β signaling. The findings suggest that clusterin inhibits melanogenesis and that it plays a role in controlling UV-induced pigmentary changes.
more목차
I. INTRODUCTION 1
II. MATERIALS AND METHODS 3
A. Cell culture 3
B. Enzyme-linked immunosorbent assay (ELISA) 3
C. Biopsy collection and immunohistochemical analysis 3
D. Lentivirus production 4
E. Preparation of the Lenti-CLU and Lenti-shCLU infected fibroblast derived concentrated conditioned medium 4
F. Melanin content and tyrosinase activity assay 5
G. Semiquantitative real-time PCR and RT-PCR 5
H. Western blot analysis 6
I. Ex vivo skin organ culture and pigmentation assay in cultured skin 7
J. Preparation of TGF type II receptor dominant negative adenovirus 7
K. Statistical analysis 8
III. RESULTS 9
1. CLU expression in aged skin and UV exposed skin. 9
2. CLU expression in skin cells and UV irradiated fibroblast. 14
3. Fibroblast derived CLU inhibits melanogenesis. 20
4. CLU inhibits pigmentation via TGF-β signaling pathway. 35
IV. DISCUSSION 40
V. REFERENCES 50
국문요약 53
