ArticleDiabetes2011
PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic β-cell apoptosis via regulation of the BH3-only protein Bim.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci.Nature communications · 2015Pooled it
- CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- PTPN2 deficiency amplifies inflammatory signalling and impairs functional maturation of human stem cell-derived islets.Stem cell research & therapy · 2026Article
- Functional recovery of islet β cells in human type 2 diabetes: Transcriptome signatures unveil therapeutic approaches.Science advances · 2025Article
- Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs of type 1 diabetes progression.Science advances · 2025Article
- Impact of genotyping (Frontiers in endocrinology · 2025Article
- A multi-ancestry genome-wide association study in type 1 diabetes.Human molecular genetics · 2024Article
- The impact of genetic variants related to vitamin D and autoimmunity: A systematic review.Heliyon · 2024Article
- PTPN2 Regulates Metabolic Flux to Affect β-Cell Susceptibility to Inflammatory Stress.Diabetes · 2024Article
- The beta cell-immune cell interface in type 1 diabetes (T1D).Molecular metabolism · 2023Review
- LncRNA ARGI Contributes to Virus-Induced Pancreatic β Cell Inflammation Through Transcriptional Activation of IFN-Stimulated Genes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- The role of the interferon/JAK-STAT axis in driving islet HLA-I hyperexpression in type 1 diabetes.Frontiers in endocrinology · 2023Review
- Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer's disease.Frontiers in neuroscience · 2023Review
- Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge.Frontiers in immunology · 2023Review
- Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines.Cell genomics · 2022Article
- Stem-Cell-Derived β-Like Cells with a Functional PTPN2 Knockout Display Increased Immunogenicity.Cells · 2022Article
- Nova1 or Bim Deficiency in Pancreatic β-Cells Does Not Alter Multiple Low-Dose Streptozotocin-Induced Diabetes and Diet-Induced Obesity in Mice.Nutrients · 2022Article
- Enhanced Wild-Type MET Receptor Levels in Mouse Hepatocytes Attenuates Insulin-Mediated Signaling.Cells · 2022Article
- Genetic overlap between type 1 diabetes and other autoimmune diseases.Seminars in immunopathology · 2022Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveGenome-wide association studies allowed the identification of several associations between specific loci and type 1 diabetes (T1D). However, the mechanisms by which most candidate genes predispose to T1D remain unclear. We presently evaluated the mechanisms by which PTPN2, a candidate gene for T1D, modulates β-cell apoptosis after exposure to type I and II interferons (IFNs), cytokines that contribute to β-cell loss in early T1D. RESEARCH DESIGN AND
methodsSmall interfering RNAs were used to inhibit PTPN2, STAT1, Bim, and Jun NH(2)-terminal kinase 1 (JNK1) expression. Cell death was assessed by Hoechst and propidium iodide staining. BAX translocation, Bim phosphorylation, cytochrome c release, and caspases 9 and 3 activation were measured by Western blot or immunofluorescence.
resultsPTPN2 knockdown exacerbated type I IFN-induced apoptosis in INS-1E, primary rat, and human β-cells. PTPN2 silencing and exposure to type I and II IFNs induced BAX translocation to the mitochondria, cytochrome c release, and caspase 3 activation. There was also an increase in Bim phosphorylation that was at least in part regulated by JNK1. Of note, both Bim and JNK1 knockdown protected β-cells against IFN-induced apoptosis in PTPN2-silenced cells.
conclusionsThe present findings suggest that local IFN production may interact with a genetic factor (PTPN2) to induce aberrant proapoptotic activity of the BH3-only protein Bim, resulting in increased β-cell apoptosis via JNK activation and the intrinsic apoptotic pathway. This is the first indication of a direct interaction between a candidate gene for T1D and the activation of a specific downstream proapoptotic pathway in β-cells.
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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.