ArticleMolecular vision2018
Epac1 deacetylates HMGB1 through increased IGFBP-3 and SIRT1 levels in the retinal vasculature.
Article in Molecular vision, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- The role of HMGB1 in vascular endothelial cells.Apoptosis : an international journal on programmed cell death · 2026Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- The mechanism of high mobility group box-1 in the proliferation and macrophage polarization in esophageal squamous cell carcinoma cells.European journal of medical research · 2025Article
- Caveolin-1 regulates inflammatory mediators in retinal endothelial cells.Molecular vision · 2024Article
- Role of High Mobility Group Box 1 in Cardiovascular Diseases.Inflammation · 2022Review
- TNFAIP3 may be key to TLR4-activation of the inflammasome in the retinal vasculature.Experimental eye research · 2022Article
- Prohibitin 1 Regulates Inflammatory Mediators and Reactive Oxygen Species in Retinal Endothelial Cells.Journal of clinical medicine · 2022Article
- PKA and Epac1 Reduce Nek7 to Block the NLRP3 Inflammasome Proteins in the Retinal Vasculature.Investigative ophthalmology & visual science · 2022Article
- TNFAIP3 is anti-inflammatory in the retinal vasculature.Molecular vision · 2022Article
- The SIRT1-HMGB1 axis: Therapeutic potential to ameliorate inflammatory responses and tumor occurrence.Frontiers in cell and developmental biology · 2022Review
- Epac1 and PKA agonists inhibit ROS to reduce NLRP3 inflammasome proteins in retinal endothelial cells.Molecular vision · 2022Article
- Epac1 Requires AMPK Phosphorylation to Regulate HMGB1 in the Retinal Vasculature.Investigative ophthalmology & visual science · 2020Article
- Article
- Epac1 and Glycyrrhizin Both Inhibit HMGB1 Levels to Reduce Diabetes-Induced Neuronal and Vascular Damage in the Mouse Retina.Journal of clinical medicine · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: Inflammation is a key component of retinal disease. We previously reported that exchange protein for cAMP 1 (Epac1) reduced inflammatory mediators, including total levels of high mobility group box 1 (HMGB1) in retinal endothelial cells (RECs) and the mouse retina. The goal of this study was to determine intermediate pathways that allow Epac1 to reduce HMGB1, which could lead to novel targets for therapeutics. Methods: We used endothelial cell-specific conditional knockout mice for Epac1 and RECs to investigate whether Epac1 requires activation of insulin like growth factor binding protein 3 (IGFBP-3) and sirtuin 1 (SIRT1) to reduce acetylated HMGB1 levels with immunoprecipitation, western blot, and enzyme-linked immunosorbent assay (ELISA). Results: Data showed that high glucose reduced IGFBP-3 and SIRT1 levels, and increased acetylation of HMGB1 in RECs. An Epac1 agonist reduced acetylated HMGB1 levels in high glucose. The Epac1 agonist could not reduce HMGB1 or SIRT1 levels when IGFBP-3 siRNA was used. The agonist also could not reduce HMGB1 when SIRT1 siRNA was used. The mouse retina showed that loss of Epac1 increases acetylated HMGB1 levels and reduces IGFBP-3 and SIRT1 levels. Conclusions: Taken together, the data suggest that Epac1 activates IGFBP-3 to increase SIRT1, leading to a significant reduction in acetylated HMGB1. These findings provide novel therapeutic targets for reducing key inflammatory cascades in the retina.
Indexed as
Identifiers
30581279PMC6279194W2901004883What OpenQuestion holds
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.