| Title: |
Targeting ATF6α Attenuates UVB ‐Induced Senescence and Improves Skin Homeostasis by Regulating IL8 Expression |
| Authors: |
Giroud, Joëlle; Delvaux, Pauline; Carlier, Laura; de Schutter, Clémentine; Martin, Nathalie; Rouget, Raphaël; Bolouki, Ayeh; de Glas, Valérie; Bouriez, Inès; Bourdoux, Florent; Burteau, Sophie; Théry, Julien; Decanter, Gauthier; Penel, Nicolas; de Launoit, Yvan; Ledoux, Benjamin; Abbadie, Corinne; Poumay, Yves; Pluquet, Olivier; Debacq‐chainiaux, Florence |
| Contributors: |
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS); Namur Research Institute for Life Sciences (NARILIS); Centre de Recherche en Automatique de Nancy (CRAN); Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS); Centre Régional de Lutte contre le Cancer Oscar Lambret Lille (UNICANCER/Lille); Université de Lille-UNICANCER; Unité de recherche en physiologie moléculaire (URPhyM); Université de Namur Namur (UNamur); This work was supported by the Institut Pasteur De Lille; Université de Namur, FSR; Ligue Contre le Cancer; Ministère de l'Enseignement Supérieur et de la Recherche Scientifique, Hubert Curien Partnership; Centre National de la Recherche Scientifique; Institut National de la Santé et de la Recherche Médicale, International Research Project (IRP); Fonds De La Recherche Scientifique – FNRS; Université de Lille. |
| Source: |
ISSN: 1474-9718. |
| Publisher Information: |
CCSD; Wiley Open Access |
| Publication Year: |
2025 |
| Collection: |
Université de Lorraine: HAL |
| Subject Terms: |
Molecular function MMPs; Narrowband NHDFs; Biological process; BP; Actinic keratoses; Ultraviolet; Unfolded protein response UV; Stress-induced premature senescence UPR; Squamous cell carcinoma SIPS; Senescence-associated β-galactosidase activity SCC; Senescence-associated secretory phenotype SA-βgal; RNA sequencing SASP; Reconstructed human epidermis RNA-seq; Principal component analysis RHE; Normal human dermal fibroblasts PCA; Cellular component; CM; Conditioned media; ECM; Extracellular matrix; ER; Endoplasmic reticulum; GO; Gene ontology; GSEA; gene set enrichment analysis; MF; Molecular function; MMPs; Matrix metalloproteinases |
| Description: |
International audience ; ABSTRACT Skin aging is influenced by both intrinsic and extrinsic factors, particularly UV radiation, and is characterized by an accumulation of senescent cells. Remarkably, exposure to UV can trigger senescence in different skin cell types, including dermal fibroblasts. However, the molecular mechanisms underlying UV‐induced senescence and the impact of the related senescence‐associated secretory phenotype (SASP) on the homeostasis of the overlying epidermis remain poorly understood. Here, we identified that both chronological aging and photoaging induce the unfolded protein response (UPR) in human dermal samples. We demonstrated that silencing ATF6α disrupts the establishment of the UVB‐induced senescent phenotype by preventing the onset of several senescent biomarkers and alters the composition of the SASP, consequently affecting its impact on the increased proliferation of keratinocytes embedded in reconstructed human epidermis. Moreover, we found that ATF6α partially mediates IL8 expression involved in the hyperproliferation of cultured keratinocytes. Together, our findings highlight the importance of the ATF6α/IL8 axis in regulating the homeostasis of neighboring cells during skin photoaging, thus suggesting ATF6α as a potentially promising target for senotherapeutic interventions. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/40241256; PUBMED: 40241256; PUBMEDCENTRAL: PMC12151886 |
| DOI: |
10.1111/acel.70024 |
| Availability: |
https://hal.science/hal-05103261; https://hal.science/hal-05103261v1/document; https://hal.science/hal-05103261v1/file/Giroud%20J%20et%20al.%202025%20Aging%20Cell.pdf; https://doi.org/10.1111/acel.70024 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.2D5FDC33 |
| Database: |
BASE |