{"doi":"10.3389/fcvm.2023.1213428","title":"TNIK regulation of interferon signaling and endothelial cell response to virus infection","abstract":"Background Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored. Methods Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs. Results Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log ( p -value) >11], downregulation of IFN-related genes, and inhibition of Hypercytokinemia/Hyperchemokinemia [-log ( p -value) >8]. The validation process encompassed qRT-PCR to evaluate mRNA expression of crucial IFN-related genes, immunoblotting to gauge STAT1 and STAT2 protein levels, and ELISA for the quantification of IFN and cytokine secretion in siTNIK-depleted ECs. These assessments consistently revealed substantial reductions upon TNIK depletion. When transducing HUVECs with replication incompetent E1-E4 deleted adenovirus expressing green fluorescent protein (Ad-GFP), it was demonstrated that TNIK depletion did not affect the uptake of Ad-GFP. Nonetheless, TNIK depletion induced cytopathic effects (CPE) in ECs transduced with wild-type human adenovirus serotype 5 (Ad-WT). Summary Our findings suggest that TNIK plays a crucial role in regulating the EC response to virus infections through modulation of the IFN pathway.","journal":"Frontiers in Cardiovascular Medicine","year":2024,"id":467039,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":315936,"name":"Abishai Dominic","orcid":null,"position":1,"is_corresponding":false},{"id":1281030,"name":"Eleanor L. Davis","orcid":null,"position":2,"is_corresponding":false},{"id":664671,"name":"Sivareddy Kotla","orcid":"0000-0001-7516-7647","position":3,"is_corresponding":false},{"id":1299924,"name":"Estefani Turcios Berrios","orcid":null,"position":4,"is_corresponding":false},{"id":1299925,"name":"Arsany Fahim","orcid":null,"position":5,"is_corresponding":false},{"id":1299926,"name":"Ashwin Arunesh","orcid":null,"position":6,"is_corresponding":false},{"id":1017735,"name":"Shengyu Li","orcid":"0000-0003-4305-6306","position":7,"is_corresponding":false},{"id":331771,"name":"Dongyu Zhao","orcid":"0000-0003-3882-0218","position":8,"is_corresponding":false},{"id":316744,"name":"Kaifu Chen","orcid":"0000-0003-1009-4357","position":9,"is_corresponding":false},{"id":1299536,"name":"Alan R. Davis","orcid":"0000-0001-7469-6205","position":10,"is_corresponding":false},{"id":886439,"name":"Minh Thi Nguyen","orcid":null,"position":11,"is_corresponding":false},{"id":963505,"name":"Yongxing Wang","orcid":"0000-0001-9665-5383","position":12,"is_corresponding":false},{"id":297875,"name":"Scott E. Evans","orcid":"0000-0003-4503-0644","position":13,"is_corresponding":false},{"id":331772,"name":"Guangyu Wang","orcid":"0000-0003-4803-7200","position":14,"is_corresponding":false},{"id":276970,"name":"John P. Cooke","orcid":"0000-0003-0033-9138","position":15,"is_corresponding":false},{"id":449040,"name":"Jun‐ichi Abe","orcid":"0000-0001-7439-7774","position":16,"is_corresponding":false},{"id":651509,"name":"David P. Huston","orcid":"0000-0002-2332-0010","position":17,"is_corresponding":false},{"id":664675,"name":"Nhat-Tu Le","orcid":"0000-0002-7664-2160","position":18,"is_corresponding":false},{"id":963504,"name":"Khanh Chau","orcid":"0000-0003-0110-5843","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:05:10.907983Z","pmid":"38264262","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":[]}