ArticleExperimental eye research2023
Blockade of interleukin-6 trans-signaling prevents mitochondrial dysfunction and cellular senescence in retinal endothelial cells.
Article in Experimental eye research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Effects of Experimental Sleep Deprivation on Peripheral Inflammation: An Updated Meta-Analysis of Human Studies.Journal of sleep research · 2026Pooled it
- Role of the DNA methyltransferases in diabetes mellitus and Its complications.Molecular biology reports · 2026Review
- Low 5HTJournal of neurochemistry · 2026Review
- Cytokines at the Crossroads of Mitochondrial Dysfunction and Inflammation in Colorectal Cancer: Implications for Postoperative Complications.Molecular diagnosis & therapy · 2026Review
- HDAC3 mediates retinal endothelial cell metabolic reprogramming and angiogenesis.Acta pharmacologica Sinica · 2026Article
- Mitochondrial dysfunction in endothelial senescence: implications for vascular remodeling and therapeutic strategies.Archives of pharmacal research · 2026Review
- The role of interleukin-6 in diabetic retinal disease: pathophysiology and therapeutic targeting.Frontiers in immunology · 2026Review
- Immune Dysregulation Connecting Type 2 Diabetes and Cardiovascular Complications.Life (Basel, Switzerland) · 2025Review
- Understanding and targeting senescence in kidney disease.Clinical kidney journal · 2025Review
- Review
- The Role of Endothelial Senescence in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2025Review
- New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.Bioengineering (Basel, Switzerland) · 2025Review
- Role of SerpinA3 in the Pathogenesis of Graves' Orbitopathy in Orbital Fibroblasts.Investigative ophthalmology & visual science · 2025Article
- IL-6 induces mitochondrial ROS production and blunts NO bioavailability in human aortic endothelial cells.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-6 (IL-6) is a multifaceted cytokine implicated in the pathogenesis of diabetic retinopathy (DR). Its activity extends through cis- and trans-signaling (TS) pathways, with cis-signaling limited to specific cell types possessing the membrane-bound IL-6 receptor, while trans-signaling broadly activates various cells without the membrane bound IL-6 receptor, including retinal endothelial cells. In this study, we determined the effects of interleukin-6 trans-signaling on mitochondrial dysfunction and cellular senescence in human retinal endothelial cells (HRECs). HRECs were cultured and treated with IL-6 + soluble IL-6R or Hyper IL-6 to activate trans-signaling, along with sgp130Fc for inhibition. RT-PCR was used to analyze gene expression changes associated with inflammation and senescence. Cellular senescence was assessed using SA β-gal staining. Mitochondrial function was evaluated using Seahorse XFe24 Bioanalyzer. IL-6 trans-signaling induced inflammatory gene expression as indicated by the upregulation of ICAM1, MCP1, and SERPINA3 levels. Additionally, it reduced mitochondrial respiration and oxidative phosphorylation, and these effects were counteracted by sgp130Fc. Moreover, IL-6 trans-signaling led to altered expression of apoptosis-associated genes, including downregulation of FIS1, BCL2, and MCL1, while promoting cellular senescence, a phenomenon mitigated by sgp130Fc. These results not only deepen our understanding of IL-6 in DR but also carry broader implications for age-related diseases and the aging process itself. This study underscores the potential therapeutic value of targeting IL-6 trans-signaling with sgp130Fc as a promising anti-inflammatory approach for DR and potentially other inflammatory conditions. Further in-vivo investigations are warranted to elucidate the function of IL-6 trans-signaling in aging-related pathologies and overall organismal health.
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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.