ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2018
PKA regulates HMGB1 through activation of IGFBP-3 and SIRT1 in human retinal endothelial cells cultured in high glucose.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- The role of HMGB1 in vascular endothelial cells.Apoptosis : an international journal on programmed cell death · 2026Review
- Nociceptor α7nAChR activation blunts neuronal HMGB1 release and attenuates inflammation and nociceptive behavior.Molecular medicine (Cambridge, Mass.) · 2025Article
- 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
- Semaphorin 7a regulates inflammatory mediators and permeability in retinal endothelial cells.Microvascular research · 2023Article
- Loss of cystatin C regulates permeability and inflammatory pathways in retina.Microvascular research · 2023Article
- Epac1 and PKA regulate of P2X7 and NLRP3 inflammasome proteins in the retinal vasculature.Experimental eye research · 2022Article
- Biochemical Functions and Clinical Characterizations of the Sirtuins in Diabetes-Induced Retinal Pathologies.International journal of molecular sciences · 2022Review
- PKA and Epac1 Reduce Nek7 to Block the NLRP3 Inflammasome Proteins in the Retinal Vasculature.Investigative ophthalmology & visual science · 2022Article
- Epac1 and PKA agonists inhibit ROS to reduce NLRP3 inflammasome proteins in retinal endothelial cells.Molecular vision · 2022Article
- Gene Expression Profile Analyses of the Skin Response of Balb/c-Nu Mice Model Injected byClinical, cosmetic and investigational dermatology · 2022Article
- The SIRT1-HMGB1 axis: Therapeutic potential to ameliorate inflammatory responses and tumor occurrence.Frontiers in cell and developmental biology · 2022Review
- Regulatory network and interplay of hepatokines, stellakines, myokines and adipokines in nonalcoholic fatty liver diseases and nonalcoholic steatohepatitis.Frontiers in endocrinology · 2022Review
- Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function.International journal of endocrinology · 2022Article
- Review
- Exosomal HMGB1 Promoted Cancer Malignancy.Cancers · 2021Article
- Expatiating the molecular approaches of HMGB1 in diabetes mellitus: Highlighting signalling pathways via RAGE and TLRs.Molecular biology reports · 2021Review
- Forskolin eye drops improve retinal damage from ischemia/reperfusion.Molecular vision · 2021Article
- Role of HMGB1 signaling in the inflammatory process in diabetic retinopathy.Cellular signalling · 2020Review
- The Complex Relationship between Diabetic Retinopathy and High-Mobility Group Box: A Review of Molecular Pathways and Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2020Review
- Review: Role of cAMP signaling in diabetic retinopathy.Molecular vision · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
OBJECTIVE AND
designInflammation is a key component of a number of diseases, including diabetic retinopathy. We investigated the cellular pathway by which protein kinase A (PKA) inhibited high mobility group box 1 (HMGB1).
methodsPrimary human retinal endothelial cells (REC) were grown in normal glucose (5 mM) or high glucose (25 mM). Cells in high glucose were treated with exchange protein for cAMP 1 (Epac1) and IGFBP-3 siRNA. Additional cells in high glucose were treated with forskolin, a PKA agonist, and Epac1 siRNA. Some cells were treated with a plasmid for insulin-like growth factor binding protein 3 (IGFBP-3) that does not bind IGF-1. Finally, some REC received Ex527, a sirtuin 1 (SIRT1) antagonist, prior to forskolin treatment. Protein analyses were done for HMGB1, Epac1, IGFBP-3, SIRT1, and PKA.
resultsPKA inhibited cytoplasmic HMGB1, independent of Epac1 actions. PKA activated IGFBP-3 and SIRT1 to inhibit cytoplasmic HMGB1. High glucose inhibited SIRT1 levels and increased cytoplasmic HMGB1 in REC.
conclusionsPKA requires active IGFBP-3 and SIRT1 to inhibit HMGB1 inflammatory actions in the retina vasculature. Activation of these pathways may offer new targets for therapy development.
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Registered trials
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