ArticleDiabetes2013
c-Jun NH2-terminal kinase 1/2 and endoplasmic reticulum stress as interdependent and reciprocal causation in diabetic embryopathy.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 76 citations in OpenAlex.
- Faf2 is required for neural differentiation in embryonic neural progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- Faf2 is required for neural differentiation in embryonic neural progenitor cells.Frontiers in cell and developmental biology · 2026Article
- Overload of Glucose Metabolism as Initiating Factor in Diabetic Embryopathy and Prevention by Glyoxalase 1 Inducer Dietary Supplement.Antioxidants (Basel, Switzerland) · 2025Article
- Article
- GLCCI1 alleviates GRP78-initiated endoplasmic reticulum stress-induced apoptosis of retinal ganglion cells in diabetic retinopathy by upregulating and interacting with HSP90AB1.Scientific reports · 2024Article
- MicroRNA-322 overexpression reduces neural tube defects in diabetic pregnancies.American journal of obstetrics and gynecology · 2024Article
- Embryonic diapause due to high glucose is related to changes in glycolysis and oxidative phosphorylation, as well as abnormalities in the TCA cycle and amino acid metabolism.Frontiers in endocrinology · 2023Article
- 4-PBA Attenuates Fat Accumulation in Cultured Spotted Seabass Fed High-Fat-Diet via Regulating Endoplasmic Reticulum Stress.Metabolites · 2022Article
- Functional cargos of exosomes derived from Flk-1Communications biology · 2022Article
- Maternal diabetes induces senescence and neural tube defects sensitive to the senomorphic rapamycin.Science advances · 2021Article
- Endoplasmic reticulum stress/XBP1 promotes airway mucin secretion under the influence of neutrophil elastase.International journal of molecular medicine · 2021Article
- MicroRNA-139-5p upregulation is associated with diabetic endothelial cell dysfunction by targeting c-jun.Aging · 2020Article
- Deficiency of the oxidative stress-responsive kinase p70S6K1 restores autophagy and ameliorates neural tube defects in diabetic embryopathy.American journal of obstetrics and gynecology · 2020Article
- Restoring BMP4 expression in vascular endothelial progenitors ameliorates maternal diabetes-induced apoptosis and neural tube defects.Cell death & disease · 2020Article
- Disturbed intracellular calcium homeostasis in neural tube defects in diabetic embryopathy.Biochemical and biophysical research communications · 2019Article
- Tip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathy.Nature communications · 2019Article
- The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy.American journal of obstetrics and gynecology · 2019Article
- Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts.Journal of cellular physiology · 2018Review
- Cellular stress and apoptosis contribute to the pathogenesis of autism spectrum disorder.Autism research : official journal of the International Society for Autism Research · 2018Article
- High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress.Stem cells and development · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Embryos exposed to high glucose exhibit aberrant maturational and cytoarchitectural cellular changes, implicating cellular organelle stress in diabetic embryopathy. c-Jun-N-terminal kinase 1/2 (JNK1/2) activation is a causal event in maternal diabetes-induced neural tube defects (NTD). However, the relationship between JNK1/2 activation and endoplasmic reticulum (ER) stress in diabetic embryopathy has never been explored. We found that maternal diabetes significantly increased ER stress markers and induced swollen/enlarged ER lumens in embryonic neuroepithelial cells during neurulation. Deletion of either jnk1 or jnk2 gene diminished hyperglycemia-increased ER stress markers and ER chaperone gene expression. In embryos cultured under high-glucose conditions (20 mmol/L), the use of 4-phenylbutyric acid (4-PBA), an ER chemical chaperone, diminished ER stress markers and abolished the activation of JNK1/2 and its downstream transcription factors, caspase 3 and caspase 8, and Sox1 neural progenitor apoptosis. Consequently, both 1 and 2 mmol/L 4-PBA significantly ameliorated high glucose-induced NTD. We conclude that hyperglycemia induces ER stress, which is responsible for the proapoptotic JNK1/2 pathway activation, apoptosis, and NTD induction. Suppressing JNK1/2 activation by either jnk1 or jnk2 gene deletion prevents ER stress. Thus, our study reveals a reciprocal causation of ER stress and JNK1/2 in mediating the teratogenicity of maternal diabetes.
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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.