ArticleDiabetes2012
Activation of endoplasmic reticulum stress by hyperglycemia is essential for Müller cell-derived inflammatory cytokine production in diabetes.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- GSK3β promotes p53/Nrf2-dependent expression of the stress response protein REDD2 in retinal Müller glia exposed to hyperlipidemic conditions.Experimental eye research · 2026Article
- Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Targeting endoplasmic reticulum stress in diabetic retinopathy: mechanistic insights and emerging therapies.Biological research · 2026Review
- Intravenous delivery of mesenchymal stromal cells reverses Müller cell endoplasmic reticulum stress in diabetic retinopathy.Stem cell research & therapy · 2025Article
- Glucose tasting depletes intracellular calcium stores and impairs macrophage functionality.iScience · 2025Article
- Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- CD40 Induces Unfolded Protein Response, Upregulation of VEGF, and Vascular Leakage in Diabetic Retinopathy.Diabetes · 2025Article
- Article
- PRDX4 mitigates diabetic retinopathy by inhibiting reactive gliosis, apoptosis, ER stress, oxidative stress, and mitochondrial dysfunction in Müller cells.The Journal of biological chemistry · 2025Article
- Targeting tRNA-Derived Non-Coding RNA Alleviates Diabetes-Induced Visual Impairment through Protecting Retinal Neurovascular Unit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Effect of Danggui Buxue decoction on hypoxia-induced injury of retinal Müller cellsEuropean journal of histochemistry : EJH · 2024Article
- α-Klotho prevents diabetic retinopathy by reversing the senescence of macrophages.Cell communication and signaling : CCS · 2024Article
- New insights into allergic rhinitis treatment: MSC nanovesicles targeting dendritic cells.Journal of nanobiotechnology · 2024Article
- Thyroid Hormone Signaling in Retinal Development and Function: Implications for Diabetic Retinopathy and Age-Related Macular Degeneration.International journal of molecular sciences · 2024Review
- Article
- Modelling neurodegeneration and inflammation in early diabetic retinopathy using 3D human retinal organoids.In vitro models · 2024Article
- Effects of Nox4 upregulation on PECAM-1 expression in a mouse model of diabetic retinopathy.PloS one · 2024Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- SRY-box transcription factor 9 modulates Müller cell gliosis in diabetic retinopathy by upregulating TXNIP transcription.Experimental animals · 2023Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Inflammation plays an important role in diabetes-induced retinal vascular leakage. The purpose of this study is to examine the role of endoplasmic reticulum (ER) stress and the signaling pathway of ER stress-induced activating transcription factor 4 (ATF4) in the regulation of Müller cell-derived inflammatory mediators in diabetic retinopathy. In diabetic animals, elevated ER stress markers, ATF4, and vascular endothelial growth factor (VEGF) expression were partially localized to Müller cells in the retina. In cultured Müller cells, high glucose induced a time-dependent increase of ER stress, ATF4 expression, and inflammatory factor production. Inducing ER stress or overexpressing ATF4 resulted in elevated intracellular adhesion molecule 1 and VEGF proteins in Müller cells. In contrast, alleviation of ER stress or blockade of ATF4 activity attenuated inflammatory gene expression induced by high glucose or hypoxia. Furthermore, we found that ATF4 regulated the c-Jun NH2-terminal kinase pathway resulting in VEGF upregulation. ATF4 was also required for ER stress-induced and hypoxia-inducible factor-1α activation. Finally, we showed that administration of chemical chaperone 4-phenylbutyrate or genetic inhibition of ATF4 successfully attenuated retinal VEGF expression and reduced vascular leakage in mice with STZ-induced diabetes. Taken together, our data indicate that ER stress and ATF4 play a critical role in retinal inflammatory signaling and Müller cell-derived inflammatory cytokine production in 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.