ArticleAmerican journal of physiology. Endocrinology and metabolism2015
ASK1 mediates the teratogenicity of diabetes in the developing heart by inducing ER stress and inhibiting critical factors essential for cardiac development.
Article in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Maternal Body Mass Index and Risk of Congenital Heart Defects in Infants: A Dose-Response Meta-Analysis.BioMed research international · 2019Pooled it
- In silico analysis of MALAT1 and H19 lncRNA interactions with the diabetes-related proteins ASK1 and YAP1.In silico pharmacology · 2026Article
- ASK1 inhibition by selonsertib attenuates elastase-induced emphysema in mice.Life sciences · 2025Article
- Small Molecule Activators of Mitochondrial Fusion Prevent Congenital Heart Defects Induced by Maternal Diabetes.JACC. Basic to translational science · 2024Article
- MicroRNA-322 overexpression reduces neural tube defects in diabetic pregnancies.American journal of obstetrics and gynecology · 2024Article
- Maternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies.International journal of molecular sciences · 2023Review
- Research Progress of Maternal Metabolism on Cardiac Development and Function in Offspring.Nutrients · 2023Review
- Single-cell transcriptomic profiling unveils dysregulation of cardiac progenitor cells and cardiomyocytes in a mouse model of maternal hyperglycemia.Communications biology · 2022Article
- Epigenetics and Congenital Heart Diseases.Journal of cardiovascular development and disease · 2022Review
- Glucose fluctuation promotes cardiomyocyte apoptosis by triggering endoplasmic reticulum (ER) stress signaling pathwayBioengineered · 2022Article
- Impact of maternal hyperglycemia on cardiac development: Insights from animal models.Genesis (New York, N.Y. : 2000) · 2021Review
- The role of glucose in physiological and pathological heart formation.Developmental biology · 2021Review
- Using Innovative Machine Learning Methods to Screen and Identify Predictors of Congenital Heart Diseases.Frontiers in cardiovascular medicine · 2021Article
- Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature.JIMD reports · 2020Article
- Restoring BMP4 expression in vascular endothelial progenitors ameliorates maternal diabetes-induced apoptosis and neural tube defects.Cell death & disease · 2020Article
- The Reciprocal Causation of the ASK1-JNK1/2 Pathway and Endoplasmic Reticulum Stress in Diabetes-Induced Cognitive Decline.Frontiers in cell and developmental biology · 2020Article
- Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes.Antioxidants (Basel, Switzerland) · 2019Review
- Maternal hyperglycemia and fetal cardiac development: Clinical impact and underlying mechanisms.Birth defects research · 2018Review
- miR-499-5p Attenuates Mitochondrial Fission and Cell Apoptosis via p21 in Doxorubicin Cardiotoxicity.Frontiers in genetics · 2018Article
- The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy.Pediatric research · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Maternal diabetes in mice induces heart defects similar to those observed in human diabetic pregnancies. Diabetes enhances apoptosis and suppresses cell proliferation in the developing heart, yet the underlying mechanism remains elusive. Apoptosis signal-regulating kinase 1 (ASK1) activates the proapoptotic c-Jun NH2-terminal kinase 1/2 (JNK1/2) leading to apoptosis, suggesting a possible role of ASK1 in diabetes-induced heart defects. We aimed to investigate whether ASK1 is activated in the heart and whether deleting the Ask1 gene blocks diabetes-induced adverse events and heart defect formation. The ASK1-JNK1/2 pathway was activated by diabetes. Deleting Ask1 gene significantly reduced the rate of heart defects, including ventricular septal defects (VSDs) and persistent truncus arteriosus (PTA). Additionally, Ask1 deletion diminished diabetes-induced JNK1/2 phosphorylation and its downstream transcription factors and endoplasmic reticulum (ER) stress markers. Consistent with this, caspase activation and apoptosis were blunted. Ask1 deletion blocked the increase in cell cycle inhibitors (p21 and p27) and the decrease in cyclin D1 and D3 and reversed diabetes-repressed cell proliferation. Ask1 deletion also restored the expression of BMP4, NKX2.5, and GATA5, Smad1/5/8 phosphorylation, whose mutations or deletion result in reduced cell proliferation, VSD, and PTA formation. We conclude that ASK1 may mediate the teratogenicity of diabetes through activating the JNK1/2-ER stress pathway and inhibiting cell cycle progression, thereby impeding the cardiogenesis pathways essential for ventricular septation and outflow tract development.
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