ArticleInternational journal of molecular sciences2019
BET Proteins Are Required for Transcriptional Activation of the Senescent Islet Cell Secretome in Type 1 Diabetes.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Article
- p21-senescent cells drive pancreatic islet dysfunction through targetable paracrine signaling in type 2 diabetes.JCI insight · 2026Article
- Pancreatic β-cell aging in physiology and diabetes: emerging roles of m6A mRNA methylation.Journal of molecular endocrinology · 2026Review
- Insulin production is sustained during DNA damage-mediated senescence in adult human beta cells.Diabetologia · 2026Article
- Syntaxin 4 protects islet β-cells from cytokine-induced senescence.Frontiers in endocrinology · 2026Article
- I-BET151 modulates glucokinase gene expression and beta cell function in part through changes in FOXO1 expression.Diabetologia · 2025Article
- Circulating senescence-associated secretory phenotype factors across the stages of type 1 diabetes in a cross-sectional cohort.Scientific reports · 2025Article
- Molecular and Inflammatory Etiologies of β-Cell Dysfunction in Type 1 Diabetes.Physiology (Bethesda, Md.) · 2025Review
- Autoreactive T Cells and Cytokine Stress Drive β-Cell Senescence Entry and Accumulation in Type 1 Diabetes.Diabetes · 2025Article
- BRD4/MAP2K7/PGF Signaling Axis Promotes Senescence and Extracellular Matrix Metabolism of Nucleus Pulposus Cells in Intervertebral Disk Degeneration.Aging cell · 2025Article
- Review
- Unlocking the secrets of aging: Epigenetic reader BRD4 as the target to combatting aging-related diseases.Journal of advanced research · 2024Review
- Article
- Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- Review
- Exploring Transcriptional Regulation of Beta Cell SASP by Brd4-Associated Proteins and Cell Cycle Control Protein p21.Epigenomes · 2024Article
- Exploring senescence as a modifier of β cell extracellular vesicles in type 1 diabetes.Frontiers in endocrinology · 2024Review
- Advances in Immunotherapeutic Approaches to Type 1 Diabetes.International journal of molecular sciences · 2023Article
- Senescence: a double-edged sword in beta-cell health and failure?Frontiers in endocrinology · 2023Article
- Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies.Frontiers in endocrinology · 2023Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Type 1 diabetes (T1D) results from the progressive loss of pancreatic beta cells as a result of autoimmune destruction. We recently reported that during the natural history of T1D in humans and the female nonobese diabetic (NOD) mouse model, beta cells acquire a senescence-associated secretory phenotype (SASP) that is a major driver of disease onset and progression, but the mechanisms that activate SASP in beta cells were not explored. Here, we show that the SASP in islet cells is transcriptionally controlled by Bromodomain ExtraTerminal (BET) proteins, including Bromodomain containing protein 4 (BRD4). A chromatin analysis of key beta cell SASP genes in NOD islets revealed binding of BRD4 at active regulatory regions. BET protein inhibition in NOD islets diminished not only the transcriptional activation and secretion of SASP factors, but also the non-cell autonomous activity. BET protein inhibition also decreased the extent of SASP induction in human islets exposed to DNA damage. The BET protein inhibitor iBET-762 prevented diabetes in NOD mice and also attenuated SASP in islet cells in vivo. Taken together, our findings support a crucial role for BET proteins in the activation of the SASP transcriptional program in islet cells. These studies suggest avenues for preventing T1D by transcriptional inhibition of SASP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.