The ribotoxic stress response drives acute inflammation, cell death, and epidermal thickening in UV-irradiated skin in vivo
Year: 2024
Type: article
Abstract: Solar UVB light causes damage to the outermost layer of skin. This insult induces rapid local responses, such as dermal inflammation, keratinocyte cell death, and epidermal thickening, all of which have traditionally been associated with DNA damage response signaling. Another stress response that is activated by UVB light is the ribotoxic stress response (RSR), which depends on the ribosome-associated mitogen-activated protein 3 kinases (MAP3K) ZAKα and culminates in p38 and JNK activation. Using ZAK knockout mice, we here show that it is the RSR that is responsible for the early manifestation of UVB-induced skin inflammation and keratinocyte death and subsequent proliferation in vivo. We also show that the RSR controls both p38-mediated pyroptotic and JNK-mediated apoptotic programmed cell death of human keratinocytes in vitro. In sum, our work highlights that skin cells rely on a cytoplasmic and ribosomal stress signal rather than a nuclear and DNA-templated signal for rapid inflammatory responses to UV exposure.
Source: Molecular Cell
Authors: Anna Constance Vind, Zhenzhen Wu, Muhammad Jasrie Firdaus, Goda Snieckute, Gee Ann Toh, Malin Jessen, José Francisco Martínez, Peter Haahr, Thomas Levin Andersen, Melanie Blasius, Li Fang Koh, Nina Loeth Maartensson, John E.A. Common, Mads Gyrd-Hansen, Franklin L. Zhong, Simon Bekker-Jensen
Institutions: University of Copenhagen, Nanyang Technological University, LEO Foundation, University of Southern Denmark, Odense University Hospital, Agency for Science, Technology and Research, Skin Research Institute of Singapore, Copenhagen University Hospital, Rigshospitalet, Newcastle University
Language: English
Topic: Skin Protection and Aging
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Funders: Harvard Medical School, Aarhus Universitet, Aarhus Universitetshospital, European Commission, National Research Foundation, Agency for Science, Technology and Research, Danmarks Grundforskningsfond, Ministry of Education, Lundbeckfonden, Jinan University, Novo Nordisk, Odense Universitetshospital, Ministry of Education, India, Novo Nordisk Fonden, LEO Fondet, Horizon 2020 Framework Programme, Medical Research Council, European Research Council, National Medical Research Council, Horizon 2020, Biomedical Research Council, H2020 European Research Council
OpenAlex ID: W4404692572