This proposal aims to assess the impact of UV exposure and aging on epidermal autophagy signalling pathway. Autophagy is a catabolic pathway crucial for cellular homeostasis. One of the main functions of the epidermis is to protect the organism from UV irradiation, which among other effects induce photo-aging and also increases the risk of disease formation including skin cancer. It is currently unknown how the autophagy in the epidermis is regulated with aging. This project will establish the mechanism affecting epidermal autophagy impairment upon chronic UV exposure and will define how this might contribute to skin photo-aging.
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2. Vitamin D improves sunburns by increasing autophagy in M2 macrophages. Das LM, Binko AM, Traylor ZP, Peng H, Lu KQ.
Autophagy. 2019 May;15(5):813-26.
3. Autophagy is induced by UVA and promotes removal of oxidized phospholipids and protein aggregates in epidermal keratinocytes. Zhao Y, et al. J Invest Dermatol 2013; 133:1629-37.
4. Concomitant inhibition of AKT and autophagy is required for efficient cisplatin-induced apoptosis of metastatic skin carcinoma. Claerhout S et al. Int J Cancer. 2010; 127(12):2790-803.
5. iASPP is a novel autophagy inhibitor in keratinocytes. Chikh A, et al, Harwood CA & Bergamaschi D. J Cell Sci. 2014; 127(14):3079-93.
6. Constitutive autophagy and nucleophagy during epidermal differentiation. Akinduro O, et al, Harwood CA, Byrne C, O’Shaughnessy RF & Bergamaschi D. J Invest Dermatol 2016;136(7):1460-70.