{"doi":"10.3390/cells13131108","title":"Bromodomain Protein Inhibition Protects β-Cells from Cytokine-Induced Death and Dysfunction via Antagonism of NF-κB Pathway","abstract":"Cytokine-induced β-cell apoptosis is a major pathogenic mechanism in type 1 diabetes (T1D). Despite significant advances in understanding its underlying mechanisms, few drugs have been translated to protect β-cells in T1D. Epigenetic modulators such as bromodomain-containing BET (bromo- and extra-terminal) proteins are important regulators of immune responses. Pre-clinical studies have demonstrated a protective effect of BET inhibitors in an NOD (non-obese diabetes) mouse model of T1D. However, the effect of BET protein inhibition on β-cell function in response to cytokines is unknown. Here, we demonstrate that I-BET, a BET protein inhibitor, protected β-cells from cytokine-induced dysfunction and death. In vivo administration of I-BET to mice exposed to low-dose STZ (streptozotocin), a model of T1D, significantly reduced β-cell apoptosis, suggesting a cytoprotective function. Mechanistically, I-BET treatment inhibited cytokine-induced NF-kB signaling and enhanced FOXO1-mediated anti-oxidant response in β-cells. RNA-Seq analysis revealed that I-BET treatment also suppressed pathways involved in apoptosis while maintaining the expression of genes critical for β-cell function, such as Pdx1 and Ins1. Taken together, this study demonstrates that I-BET is effective in protecting β-cells from cytokine-induced dysfunction and apoptosis, and targeting BET proteins could have potential therapeutic value in preserving β-cell functional mass in T1D.","journal":"Cells","year":2024,"id":468383,"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":0.9522,"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":330423,"name":"Jeongkyung Lee","orcid":null,"position":1,"is_corresponding":false},{"id":709481,"name":"Varun Mandi","orcid":null,"position":2,"is_corresponding":false},{"id":565259,"name":"Joseph Danvers","orcid":null,"position":3,"is_corresponding":false},{"id":564347,"name":"Ruya Liu","orcid":"0000-0003-1986-6800","position":4,"is_corresponding":false},{"id":564351,"name":"Eliana Melissa Perez-Garcia","orcid":"0000-0002-3185-9649","position":5,"is_corresponding":false},{"id":245728,"name":"Feng Li","orcid":"0000-0002-9680-4614","position":6,"is_corresponding":false},{"id":586271,"name":"Rajaganapati Jagannathan","orcid":null,"position":7,"is_corresponding":false},{"id":564350,"name":"Ping Yang","orcid":"0000-0003-3021-8409","position":8,"is_corresponding":false},{"id":1301118,"name":"Domenic Filingeri","orcid":"0000-0003-2713-4335","position":9,"is_corresponding":false},{"id":1301119,"name":"Amit Kumar","orcid":"0000-0003-0195-233X","position":10,"is_corresponding":false},{"id":329470,"name":"Ke Ma","orcid":"0000-0002-5206-1038","position":11,"is_corresponding":false},{"id":564353,"name":"Mousumi Moulik","orcid":"0009-0007-8705-4181","position":12,"is_corresponding":false},{"id":60611,"name":"Vijay Yechoor","orcid":"0000-0002-9981-6784","position":13,"is_corresponding":false},{"id":469765,"name":"Vinny Negi","orcid":"0000-0003-3120-6952","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:05:19.071498Z","pmid":"38994961","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":[]}