Autophagy Stimulation Upregulated Collagen Synthesis in Cultured Human Fibroblast = Autophagy Stimulation Upregulated Collagen Synthesis in Cultured Human Fibroblast

다국어 초록 (Multilingual Abstract)

Autophagy can be defined as a self-digestive process, targeting internal or damaged organelles and misfolded proteins to lysosomal degradation. While its major role is a survival mechanism under stress conditions, such as nutrient restriction, it can also affect various cellular responses including inflammation, aging, and immune responses. Along with the clinical implications in various human diseases, such as neurodegenerative diseases, infection, and cancer, recent reports also suggested the potential involvement of autophagy in skin aging. In order to investigate the roles of autophagy in skin physiology, amino acid based chemical library was established and potential autophagy stimulating compounds were identified by measuring autophagic vacuole formation in cultured human fibroblast. Upregulation of autophgic flux by screened compounds were further investigated by measuring p62 and LC3-II expressions. Electron microscopic observation was also performed for observing the morphologic changes in cells. Among the screened compounds, S8_049, and S9_067 showed significant stimulating activities in cultured human skin fibroblast. In order to investigate the potential anti-aging effects of the selected compounds, expression of collagen and MMPs were also measured in cultured fibroblasts. As results, increased expression of collagen I was observed in S8_049 treated cells. Full thickness 3D culture model experiments also confirmed the increased expression of collagens in dermal layer in S8_049 treated tissue. Microarray experiments showed the increased expression of several sphingolipids synthesis and degrading enzymes, which suggested that the changes of intracellular sphingolipids levels might be, at least in part, underlying mechanism of autophagy stimulation.