Target identification research on the adiponectin-secreting activity of kojyl cinnamate derivatives in human mesenchymal stem cells
사람의 중간엽줄기세포에서 아디포넥틴 분비촉진 효과를 나타내는 코질신나메이트 유도체들의 타겟 규명 연구
- Minsoo Noh
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- Human adipose tissue-derived mesenchymal stem cells; Phenotype-based screening; Target deconvolution; Adipogenesis; Adiponectin; Peroxisome proliferator-activated receptor
- 학위논문 (석사)-- 서울대학교 대학원 약학대학 약학과, 2017. 8. Minsoo Noh.
- Human mesenchymal stem cells (hMSCs) possess the capacity for multi-lineage differentiation. Under the appropriate conditions, hMSCs can undergo cell fate decision to commit to adipogenic, osteogenic, chondrogenic, or myogenic lineages. In this regard, the adipogenesis of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) can be used as a model for phenotype-based screening of anti-aging skin compounds with lipofilling effects.
The kojyl cinnamate derivative, Seletinoid G, has been clinically proven to have anti-aging effects in human skin. However, the efficacy in the phenotype assay was not sufficient to perform molecular target identification research. In this study, we developed novel kojyl cinnamate derivatives for improved adiponectin promoting activity in hAT-MSCs. Through target deconvolution, we found that the adiponectin-secreting activities of kojyl cinnamates were correlated with PPARγ and PPARα, but not PPARδ activation. In a further investigation, we found that kojyl cinnamates with high binding affinities towards PPARγ and PPARα significantly increased the expressions of cholesterol and fatty acid synthesizing enzymes in both hAT-MSCs and primary normal human keratinocytes (NHKs). Our findings suggest that kojyl cinnamate derivatives with PPARγ and PPARα dual agonism have the potential to repair altered skin barrier function and improve aged-related decrease of subcutaneous adipose tissue.