ArticleDiabetologia2010
Deficiency of Atf3, an adaptive-response gene, protects islets and ameliorates inflammation in a syngeneic mouse transplantation model.
Article in Diabetologia, 2010. 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, 55 citations in OpenAlex.
- The Downregulation of Type 1 Diabetes Susceptibility Gene PGM1 Induces Metabolic Imbalance and Stress in Pancreatic β-Cells.Diabetes · 2026Article
- Molecular profiling of NOD mouse islets reveals a novel regulator of insulitis onset.Scientific reports · 2024Article
- Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40.EMBO reports · 2023Article
- Mitophagy as a mitochondrial quality control mechanism in myocardial ischemic stress: from bench to bedside.Cell stress & chaperones · 2023Review
- Activating transcription factor 3, glucolipid metabolism, and metabolic diseases.Journal of molecular cell biology · 2023Article
- Advancements in innate immune regulation strategies in islet transplantation.Frontiers in immunology · 2023Review
- Genetic loss-of-function of activating transcription factor 3 but not C-type lectin member 5A prevents diabetic peripheral neuropathy.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Master Regulator Activating Transcription Factor 3 (ATF3) in Metabolic Homeostasis and Cancer.Frontiers in endocrinology · 2020Review
- Human Islet Response to Selected Type 1 Diabetes-Associated Bacteria: A Transcriptome-Based Study.Frontiers in immunology · 2019Article
- Activating transcription factor 3 modulates protein kinase C epsilon activation in diabetic peripheral neuropathy.Journal of pain research · 2019Article
- Nano-Encapsulation of Bilirubin in Pluronic F127-Chitosan Improves Uptake in β Cells and Increases Islet Viability and Function after Hypoxic Stress.Cell transplantation · 2017Article
- Activating transcription factor 3 in immune response and metabolic regulation.Liver research (Beijing, China) · 2017Article
- Physiologic Doses of Bilirubin Contribute to Tolerance of Islet Transplants by Suppressing the Innate Immune Response.Cell transplantation · 2017Article
- Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury.Open biology · 2016Article
- Lipotoxic brain microvascular injury is mediated by activating transcription factor 3-dependent inflammatory and oxidative stress pathways.Journal of lipid research · 2016Article
- The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes.Nature medicine · 2015Article
- A systems biology analysis of brain microvascular endothelial cell lipotoxicity.BMC systems biology · 2014Article
- Article
- Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus.Sleep · 2013Article
- ATF3 expression in the corpus luteum: possible role in luteal regression.Molecular endocrinology (Baltimore, Md.) · 2013Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
aims/hypothesisIslet transplantation is a potential therapeutic option for type 1 diabetes. However, the need for multiple donors per patient and heavy immunosuppression of the recipients limit its use. The goal of this study was to test whether the gene encoding activating transcription factor 3 (ATF3), a stress-inducible pro-apoptotic gene, plays a role in graft rejection in islet transplantation.
methodsWe compared wild-type (WT) and Atf3 knockout (KO) islets in vitro using stress paradigms relevant to islet transplantation: isolation, inflammation and hypoxia. We also compared the WT and KO islets in vivo using a syngeneic mouse transplantation model.
resultsATF3 was induced in all three stress paradigms and played a deleterious role in islet survival, as evidenced by the lower viability of WT islets compared with KO islets. ATF3 upregulated various downstream target genes in a stress-dependent manner. These target genes can be classified into two functional groups: (1) apoptosis (Noxa [also known as Pmaip1] and Bnip3), and (2) immunomodulation (Tnfalpha [also known as Tnf], Il-1beta [also known as Il1b], Il-6 [also known as Il6] and Ccl2 [also known as Mcp-1]). In vivo, Atf3 KO islets performed better than WT islets after transplantation, as evidenced by better glucose homeostasis in the recipients and the reduction of the following variables in the KO grafts: caspase 3 activation, macrophage infiltration and expression of the above apoptotic and immunomodulatory genes. CONCLUSIONS/
interpretationATF3 plays a role in islet graft rejection by contributing to islet cell death and inflammatory responses at the graft sites. Silencing the ATF3 gene may provide therapeutic benefits in islet transplantation.
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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.