{"doi":"10.1016/j.jpap.2025.100265","title":"Targeting β2-adrenergic receptor reduces UV-induced cutaneous damage and inflammation in a murine model","abstract":"Preclinical studies demonstrated that the β-adrenergic receptor antagonists (β-blockers) inhibit skin damage and cancer development induced by ultraviolet (UV) radiation, but the mechanism remains unknown. β2-adrenergic receptor (β2-AR) is the predominant adrenergic receptor expressed on skin keratinocytes and immune cells that bind to catecholamines, but its function in UV-induced skin lesions is unknown. Here, the role of β2-AR in UV-induced acute skin damage was investigated using a β2-AR knockout (KO) mouse model. The β2-AR KO mice exhibited attenuated UV-induced skin edema, sunburn, erythema, barrier disruption, apoptosis, and overexpression of IL-6, accompanied by a transient elevation in expression of β1- and β3-ARs. Cytokine array and immunohistochemical analysis of the KO skin revealed reduced UV-induced overexpression of multiple cytokines and chemokines involved in leukocyte infiltration and inflammation. RNA-sequencing analysis confirms that UV triggers a differential transcriptional response between the WT and KO skin. Furthermore, RNA-sequencing identified multiple gene regulatory pathways involved in the KO skin, including reduced activity of the pro-inflammatory transcription factor NF-κB, increased activity of Interferon Response Factors (IRFs) and the glucocorticoid receptor (GR), and reductions in myeloid immune cell/macrophage-related signaling pathways such as CEBP-β and GATA transcription factors. Collectively, these gene regulatory alterations were associated with a substantial reduction in innate immune, inflammatory, and mesenchymal tissue differentiation responses to the UV radiation in the KO skin. These data identify β2-AR as a critical neurobiological pathway involved in UV-induced skin damage and inflammation and support that β2-AR blockade might be useful for preventing UV-related skin lesions and sequelae (e.g., cancers).","journal":"Journal of Photochemistry and Photobiology","year":2025,"id":553033,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1150850,"name":"Rita Miwalian","orcid":"0009-0003-2669-4047","position":1,"is_corresponding":false},{"id":371733,"name":"Bradley T. Andresen","orcid":"0000-0002-3948-7456","position":2,"is_corresponding":false},{"id":335231,"name":"Steve W. Cole","orcid":"0000-0002-7168-8039","position":3,"is_corresponding":false},{"id":371734,"name":"Ying Huang","orcid":"0000-0003-4756-7939","position":4,"is_corresponding":false},{"id":372922,"name":"Ayaz Shahid","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:37.527189Z","pmid":"41890982","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}