{"doi":"10.1007/s10565-024-09968-0","title":"JAG1 mediates apoptosis in herpes simplex keratitis by suppressing autophagy via ROS/JAG1/NOTCH1/pULK1 signaling pathway","abstract":null,"journal":"Cell Biology and Toxicology","year":2024,"id":633322,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":653625,"name":"Yao Yao","orcid":"0000-0001-6058-3007","position":1,"is_corresponding":false},{"id":1641915,"name":"Xinghong Sun","orcid":null,"position":2,"is_corresponding":false},{"id":820644,"name":"Wenzhe Wang","orcid":"0000-0001-8967-6581","position":3,"is_corresponding":false},{"id":1641917,"name":"Haochen Qian","orcid":null,"position":4,"is_corresponding":false},{"id":1641919,"name":"Yumeilan Liu","orcid":"0000-0002-1039-8724","position":5,"is_corresponding":false},{"id":1641921,"name":"Chunyan Xue","orcid":"0000-0001-9601-2011","position":6,"is_corresponding":false},{"id":1472714,"name":"Wei Ye","orcid":"0000-0003-0360-7900","position":7,"is_corresponding":false},{"id":544042,"name":"Feng Jiang","orcid":"0000-0003-3244-1604","position":8,"is_corresponding":false},{"id":1641913,"name":"Jingyao Chang","orcid":"0000-0002-3443-7230","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"JAG1 mediates apoptosis in herpes simplex keratitis by suppressing autophagy via ROS/JAG1/NOTCH1/pULK1 signaling pathway","abstract":"Herpes simplex keratitis (HSK), an ocular disease resulted from herpes simplex virus type 1 (HSV-1) infection, leads to the majority of infectious corneal blindness worldwide. The apoptosis of corneal epithelial cells (CECs) resulted from HSV-1 disrupts the epithelial barrier and exacerbates the infection; however, there is no definitive cure for HSK. Jagged1 (JAG1), one of the primary functional ligands for NOTCH receptors, plays a crucial role in regulating apoptosis and autophagy; however, its role in HSK is unclear. Our transcriptome analysis showed JAG1 was significantly upregulated in HSV-1-infected human CECs. We aimed to explore JAG1's role in regulating apoptosis in HSV-1-infected human CECs and in HSK mice. HSV-1 infection induced apoptosis and reactive oxygen species (ROS) generation in CECs. HSV-1 also activated the JAG1/NOTCH1 signaling pathway. The ROS scavenger N-acetylcysteine significantly mitigated these effects. Additionally, inhibiting the JAG1/NOTCH1 pathway with short hairpin RNA against JAG1 or a NOTCH1 inhibitor (N-[N-{3,5-difuorophenacetyl}-1-alanyl]-S-phenylglycine t-butyl ester [DAPT]) alleviated HSV-1-induced CEC apoptosis. Transmission electron microscopy and western blotting revealed that HSV-1 infection suppressed ULK1-mediated autophagy in CECs, while DAPT treatment enhanced autophagy by suppressing ULK1 phosphorylation. The activation of autophagy by rapamycin treatment markedly reduced ROS levels and apoptosis in HSV-1-infected CECs, revealing a synergistic effect between the suppressed autophagy and increased ROS levels, ultimately leading to apoptosis. Thus, HSV-1 induces CEC apoptosis by suppressing autophagy through ROS/JAG1/NOTCH1/pULK1 signaling pathway in vitro and in vivo, providing potential therapeutic targets for HSK.","is_dataset_classified":null,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39704867","pmcid":"PMC11662045","openalex_id":"https://openalex.org/W4405616582","authors":[],"funders":[{"funder_name":"Jinling Hospital foundation project","grant_id":"2023YYHLZX182","title":null},{"funder_name":"Special Fund for Clinical Research of Nanjing Drum Tower Hospital","grant_id":"2024-LCYJ-MS-26","title":null}],"total_grants":2,"fwci":7.4098,"citation_percentile":0.98550193,"influential_citations":0,"citation_trend":[{"year":2025,"count":11},{"year":2026,"count":7}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1007/s10565-024-09968-0","host_type":"journal"},{"url":"https://doi.org/10.1007/s10565-024-09968-0","host_type":"publisher"},{"url":"https://link.springer.com/content/pdf/10.1007/s10565-024-09968-0.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s10565-024-09968-0/fulltext.html","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39704867","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11662045","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11662045","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11662045?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Toxoplasma gondii Research Studies","interferon and immune responses","Ocular Diseases and Behçet’s Syndrome","Receptor, Notch1","Jagged-1 Protein","Animals","Apoptosis","Reactive Oxygen Species","Autophagy","Signal Transduction","Humans","Keratitis, Herpetic","Mice","Herpesvirus 1, Human","Female","Epithelial Cells"],"mesh_terms":["Jagged-1 Protein","Animals","Autophagy","Epithelial Cells","Female","Humans","Signal Transduction","Keratitis, Herpetic","Apoptosis","Reactive Oxygen Species","Herpesvirus 1, Human","Mice","Receptor, Notch1"],"keywords":["Autophagy","JAG1","Apoptosis","Reactive oxygen species","Signal transduction","Biology","Herpes simplex virus","Cancer research","Cell biology","Downregulation and upregulation","ATG5","Chemistry","Immunology","Notch signaling pathway","Biochemistry","Virus","Corneal Epithelial Cell"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T11:49:51.308959Z","pmid":null,"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":[]}