{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305019/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305019"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"C/EBPβ Deficiency Enhances Keratinocyte Apoptosis after UVB-Induced DNA Damage via Regulation of the Type I IFN and TNF Responses","description":"The epidermis is routinely subjected to DNA damage induced by solar (UVB) radiation. In addition to activating canonical DNA damage responses such as cycle cell checkpoints and DNA repair, UVB-induced DNA damage can also activate additional signaling pathways including inflammatory responses. The pathways activated downstream of UVB-induced DNA damage have a critical role in determining cellular survival to UVB radiation. Here we report that loss of CCAAT-enhancer/binding protein β (C/EBPβ) in mouse keratinocytes results in enhanced UVB-induced apoptosis through activation of extrinsic apoptosis genes cleaved caspase-8 and tBid. RNAseq and Ingenuity Pathway Analysis of UVB-treated C/EBPβ-/- primary keratinocytes revealed an enrichment of inflammatory signaling pathways, including the type I interferon (IFN-I) pathway as the most enriched pathway. Numerous IFN-I stimulated genes were up-regulated in UVB-treated C/EBPβ-/- keratinocytes, including genes that regulate extrinsic apoptosis. Inhibition of the interferon / receptor or the associated kinase Tyk2 greatly reduced cell death in UVB-exposed C/EBPβ deficient keratinocytes, demonstrating the dependence of IFN signaling in C/EBPβ regulated apoptosis. The apoptosis inducing cytokine, tumor necrosis factor alpha (TNF-α) was identified as one of the most significant upstream regulators activated in UVB exposed C/EBPβ-/- keratinocytes compared to UVB exposed wild type control. UVB exposed C/EBPβ-/- keratinocytes displayed increased expression of TNF-α and the enhanced apoptosis in C/EBPβ-/- keratinocytes was suppressed by a TNF-α neutralizing antibody. Our results indicate that loss of C/EBPβ enhances activation of a non-canonical UVB DNA damage response pathway involving interferon and TNF signaling to induce keratinocyte cell death.","dates":{"publication":"2026/04/01"},"accession":"GSE305019","cross_references":{"GSM":["GSM9161161","GSM9161163","GSM9161155","GSM9161154","GSM9161157","GSM9161159"],"GPL":["17021"],"GSE":["305019"],"taxon":["Mus musculus"],"PMID":["[41878233]"]}}