ArticleCellular signalling2012
TNFα and SOCS3 regulate IRS-1 to increase retinal endothelial cell apoptosis.
Article in Cellular signalling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 59 citations in OpenAlex.
- Elevating Jak-STAT signaling via SOCS3 deletion sustains photoreceptor viability and visual function in mouse models of retinitis pigmentosa.Cell communication and signaling : CCS · 2026Article
- Transcriptomic responses and molecular mechanisms of glucagon-regulated glucose metabolism in Japanese flounder (Frontiers in physiology · 2026Article
- Cytokeratin 8 as a Novel Therapeutic Target in Type 2 Diabetes Mellitus: Suppression of Hepatic Glycogen Synthesis via IRS1/PI3K/Akt/GSK3β Signaling.Current drug targets · 2026Article
- Modulation of microglial phagocytosis via the GAS6-MERTK pathway regulates pathological angiogenesis in the mouse oxygen-induced retinopathy model.Cell death & disease · 2025Article
- Article
- EphB1 causes retinal damage through inflammatory pathways in the retina and retinal Müller cells.Molecular vision · 2024Article
- Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy.Cell death discovery · 2023Review
- Long Non-coding RNA SPAG5-AS1 Attenuates Diabetic Retinal Vascular Dysfunction by Inhibiting Human Retinal Microvascular Endothelial Cell Proliferation, Migration, and Tube Formation by Regulating the MicroRNA-1224-5p/IRS-1 Axis.Molecular biotechnology · 2023Article
- Article
- Potential Biomarkers and Drugs for Nanoparticle-Induced Cytotoxicity in the Retina: Based on Regulation of Inflammatory and Apoptotic Genes.International journal of environmental research and public health · 2022Article
- Genome-Wide Transcriptome Analysis in Type 2 Diabetes Patients Treated by Sitagliptin.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Insulin Signal Transduction is Impaired in the Type 2 Diabetic Retina.Journal of diabetes and clinical research · 2020Article
- Blockade of insulin receptor substrate-1 inhibits biological behavior of choroidal endothelial cells.International journal of ophthalmology · 2019Article
- miR15a regulates NLRP3 inflammasome proteins in the retinal vasculature.Experimental eye research · 2018Article
- HMGB1 inhibits insulin signalling through TLR4 and RAGE in human retinal endothelial cells.Growth factors (Chur, Switzerland) · 2018Article
- miRNA15a regulates insulin signal transduction in the retinal vasculature.Cellular signalling · 2018Article
- Epac1 Restores Normal Insulin Signaling through a Reduction in Inflammatory Cytokines.Mediators of inflammation · 2018Article
- Toll-like receptor 4 regulates insulin signal transduction in retinal Müller cells.Growth factors (Chur, Switzerland) · 2017Article
- TLR4 regulates insulin-resistant proteins to increase apoptosis in the mouse retina.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- miR-146a suppresses STAT3/VEGF pathways and reduces apoptosis through IL-6 signaling in primary human retinal microvascular endothelial cells in high glucose conditions.Vision research · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Rates of diabetes are reaching epidemic levels. The key problem in both type 1 and type 2 diabetes is dysfunctional insulin signaling, either due to lack of production or due to impaired insulin sensitivity. A key feature of diabetic retinopathy in animal models is degenerate capillary formation. The goal of this present study was to investigate a potential mechanism for retinal endothelial cell apoptosis in response to hyperglycemia. The hypothesis was that hyperglycemia-induced TNFα leads to retinal endothelial cell apoptosis through inhibition of insulin signaling. To test the hypothesis, primary human retinal endothelial cells were grown in normal glucose (5 mM) or high glucose (25 mM) and treated with exogenous TNFα, TNFα siRNA or suppressor of cytokine signaling 3 (SOCS3) siRNA. Cell lysates were processed for Western blotting and ELISA analyses to verify TNFα and SOCS3 knockdown, as well as key pro- and anti-apoptotic factors, IRS-1, and Akt. Data indicate that high glucose culturing conditions significantly increase TNFα and SOCS3 protein levels. Knockdown of TNFα and SOCS3 significantly increases anti-apoptotic proteins, while decreasing pro-apoptotic proteins. Knockdown of TNFα leads to decreased phosphorylation of IRS-1(Ser307), which would promote normal insulin signaling. Knockdown of SOCS3 increased total IRS-1 levels, as well as decreased IR(Tyr960), both of which would inhibit retinal endothelial cell apoptosis through increased insulin signaling. Taken together, our findings suggest that increased TNFα inhibits insulin signaling in 2 ways: 1) increased phosphorylation of IRS-1(Ser307), 2) increased SOCS3 levels to decrease total IRS-1 and increase IR(Tyr960), both of which block normal insulin signal transduction. Resolution of the hyperglycemia-induced TNFα levels in retinal endothelial cells may prevent apoptosis through disinhibition of insulin receptor signaling.
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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.