1490 Autophagy-inducing “osmo-patch” for skin regeneration by activation of the calcium condensate-dependent CaMKKβ-AMPK-ULK axis

Autophagy is a major catabolic mechanism that essential for skin homeostasis. Improving autophagy critical dermal research since this process impaired during aging, wounding, or diseases such as atopic dermatitis. Although hyperosmotic stress has been shown to stimulate autophagy, there still lack of understanding the underlying action, well need expand possible implementations knowledge. Here, by utilizing sugars, we investigated pathway which induces in and developed functional “osmo-patch” autophagy-based regeneration. was confirmed treatment primary human fibroblasts with various disaccharides trisaccharides, led conversion LC3I LC3II autophagosome formation, marked increased LC3-positive puncta. It also sugar could induce other cells, including keratinocytes melanocytes, dorsal mouse model. Holotomographic analysis revealed generates intracellular calcium condensates. Calcium-dependent gene CaMKKβ siRNA depletion decreased phosphorylation AMPK ULK1 (S555), while promoted it. Additionally, chelator EGTA inhibitor dorsomorphin inhibited same proteins, indicating involvement condensate-dependent CaMKKβ-AMPK-ULK axis activating stress-induced autophagy. Lastly, confirm applicability our findings, consideration current global demand natural materials, an hydrogel formulated disaccharide trehalose applied dermatitis-like model sensitized H2O2. Treatment successfully improved ameliorated pathogenic symptoms, showing potential clinical application.