S-Space College of Agriculture and Life Sciences (농업생명과학대학) Dept. of Agricultural Biotechnology (농생명공학부) Theses (Master's Degree_농생명공학부)
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
- 농업생명과학대학 농생명공학부
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2014. 8. 이기원.
- 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.