ArticleExperimental cell research2013
Critical role of TXNIP in oxidative stress, DNA damage and retinal pericyte apoptosis under high glucose: implications for diabetic retinopathy.
Article in Experimental cell research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 114 citations in OpenAlex.
- Crosstalk Between Nrf2 and Metabolic Pathways: Redox Regulation, Glutaminolysis, and Cellular Proliferation.Cell biochemistry and biophysics · 2026Review
- Tempol Attenuates Diabetes-induced Transcriptomic Changes in the Rat Retina.Molecular neurobiology · 2026Article
- Metabolic Dysregulation and Oxidative Stress in Diabetic Retinopathy: Glycogen Metabolism, Mitochondrial Dysfunction, and Antioxidant Defences.Antioxidants (Basel, Switzerland) · 2026Review
- The Effects of Coenzyme Q10 Supplementation on the Contrast Sensitivity Score, Biomarkers of Oxidative Stress, Inflammation, and β-Secretase Activity in the Blood and the Correlation Among these Factors in Diabetic Retinopathy Patients; Clinical Trial.Advanced pharmaceutical bulletin · 2026Article
- Metabolic reprogramming in diabetic complications: mechanisms, pathologies, and molecular evidence from multi-organ studies.Frontiers in immunology · 2026Review
- When Mitochondria Falter, the Barrier Fails: Mechanisms of Inner Blood-Retinal Barrier (iBRB) Injury and Opportunities for Mitochondria-Targeted Repair.International journal of molecular sciences · 2025Review
- DJ-1 Protects Human Retinal Endothelial Cells From Diabetes-Related Conditions and Prevents Ischemic Damage in Mouse Retinal Capillaries.Investigative ophthalmology & visual science · 2025Article
- STAT3 expression is reduced in cardiac pericytes in HFpEF and its loss reduces cellular adhesion and induces pericyte senescence.FEBS letters · 2025Article
- NMN Supplementation Inhibits Endothelial Cell ROS-Mediated Src/Pi3k/Akt Signaling Pathway to Protect High-Altitude Blood-Retinal Barrier.Investigative ophthalmology & visual science · 2025Article
- Glucose fluctuations aggravate cardiomyocyte apoptosis by enhancing the interaction between Txnip and Akt.BMC cardiovascular disorders · 2024Article
- Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy.Frontiers in endocrinology · 2024Review
- Article
- Resveratrol improves diabetes-induced cognitive dysfunction in part through the miR-146a-5p/TXNIP axis.The Kaohsiung journal of medical sciences · 2023Article
- The application and progression of CRISPR/Cas9 technology in ophthalmological diseases.Eye (London, England) · 2023Review
- Changes in the Expression Profile of Pyroptosis-Related Genes in Senescent Retinal Pigment Epithelial Cells after Lutein Treatment.Current issues in molecular biology · 2023Article
- Prognostic value of choroidal vascular index in determining response to intravitreal dexamethasone implant treatment used in refractory diabetic macular edema.Lasers in medical science · 2023Article
- Review
- Thioredoxin-Interacting Protein in Cancer and Diabetes.Antioxidants & redox signaling · 2022Review
- IL-10 Dysregulation Underlies Chemokine Insufficiency, Delayed Macrophage Response, and Impaired Healing in Diabetic Wounds.The Journal of investigative dermatology · 2022Article
- Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy.Frontiers in neuroscience · 2022Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Diabetic retinopathy (DR) is characterized by early loss of retinal capillary pericytes and microvascular dysfunction. We recently showed that pro-oxidative stress and pro-apoptotic thioredoxin interacting protein (TXNIP) is significantly up-regulated in rat retinas in experimental diabetes and mediates inflammation and apoptosis. Therefore, we hypothesize here that TXNIP up-regulation in pericyte plays a causative role in oxidative stress and apoptosis under sustained high glucose exposure in culture. We maintained a rat retinal capillary pericyte cell line (TR-rPCT1) for 5 days under low glucose (LG, 5.5mM) or high glucose (HG, 25 mM) with or without anti-oxidant N-acetylcysteine (5mM, NAC), Azaseine (2 μM, AzaS), an inhibitor of TXNIP, and TXNIP siRNA (siTXNIP3, 20 nM). The results show that HG increases TXNIP expression in TR-rPCT1, which correlates positively with ROS generation, protein S-nitrosylation, and pro-apoptotic caspase-3 activation. Furthermore, pericyte apoptosis is demonstrated by DNA fragmentation (alkaline comet assay) and a reduction in MTT survival assay. Treatment of TR-rPCT1 with NAC or an inhibition of TXNIP by AzaS or siTXNIP3 each reduces HG-induced ROS, caspase-3 activation and DNA damage demonstrating that TXNIP up-regulation under chronic hyperglycemia is critically involved in cellular oxidative stress, DNA damage and retinal pericyte apoptosis. Thus, TXNIP represents a novel gene and drug target to prevent pericyte loss and progression of DR.
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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.