ArticleThe Journal of experimental medicine1999
A20 inhibits cytokine-induced apoptosis and nuclear factor kappaB-dependent gene activation in islets.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 212 citations in OpenAlex.
- Identification of novel regulators in T-cell differentiation of aplastic anemia patients.BMC genomics · 2006Trial
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- RELA governs a network of islet-specific metabolic genes necessary for beta cell function.Diabetologia · 2023Article
- Prevention of Type 1 Diabetes in Children: A Worthy Challenge?International journal of environmental research and public health · 2023Review
- Compound A attenuates proinflammatory cytokine-induced endoplasmic reticulum stress in beta cells and displays beneficial therapeutic effects in a mouse model of autoimmune diabetes.Cellular and molecular life sciences : CMLS · 2022Article
- TNFAIP3 is anti-inflammatory in the retinal vasculature.Molecular vision · 2022Article
- Transcript Expression Profiles and MicroRNA Regulation Indicate an Upregulation of Processes Linked to Oxidative Stress, DNA Repair, Cell Death, and Inflammation in Type 1 Diabetes Mellitus Patients.Journal of diabetes research · 2022Article
- Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- A zebrafish functional genomics model to investigate the role of human A20 variants in vivo.Scientific reports · 2020Article
- Article
- Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges.Cell stem cell · 2018Review
- Computing of Low Shear Stress-Driven Endothelial Gene Network Involved in Early Stages of Atherosclerotic Process.BioMed research international · 2018Article
- The Fate of Allogeneic Pancreatic Islets following Intraportal Transplantation: Challenges and Solutions.Journal of immunology research · 2018Review
- MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD.JCI insight · 2017Article
- Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis.Genes · 2017Review
- The Nexus of Stem Cell-Derived Beta-Cells and Genome Engineering.The review of diabetic studies : RDS · 2017Review
- CRISPR/Cas9-mediated knockout of c-REL in HeLa cells results in profound defects of the cell cycle.PloS one · 2017Article
- A20 reduces lipid storage and inflammation in hypertrophic adipocytes via p38 and Akt signaling.Molecular and cellular biochemistry · 2016Article
- Hypothermic machine perfusion increases A20 expression which protects renal cells against ischemia/reperfusion injury by suppressing inflammation, apoptosis and necroptosis.International journal of molecular medicine · 2016Article
- A20 deficiency leads to angiogenesis of pulmonary artery endothelial cells through stronger NF-κB activation under hypoxia.Journal of cellular and molecular medicine · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease resulting from apoptotic destruction of beta cells in the islets of Langerhans. Low expression of antioxidants and a predilection to produce nitric oxide (NO) have been shown to underscore beta cell apoptosis. With this perspective in mind, we questioned whether beta cells could mount an induced protective response to inflammation. Here we show that human and rat islets can be induced to rapidly express the antiapoptotic gene A20 after interleukin (IL)-1beta activation. Overexpression of A20 by means of adenovirus-mediated gene transfer protects islets from IL-1beta and interferon gamma-induced apoptosis. The cytoprotective effect of A20 against apoptosis correlates with and is dependent on the abrogation of cytokine-induced NO production. The inhibitory effect of A20 on cytokine-stimulated NO production is due to transcriptional blockade of inducible NO synthase (iNOS) induction; A20 inhibits the activation of the transcription factor nuclear factor kappaB at a level upstream of IkappaBalpha degradation. These data demonstrate a dual antiapoptotic and antiinflammatory function for A20 in beta cells. This qualifies A20 as part of the physiological cytoprotective response of islets. We propose that A20 may have therapeutic potential as a gene therapy candidate to achieve successful islet transplantation and the cure of IDDM.
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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.