ArticleBiochimica et biophysica acta2014
Pro-inflammatory cytokines downregulate Hsp27 and cause apoptosis of human retinal capillary endothelial cells.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- DJ-1 Protects Human Retinal Endothelial Cells From Diabetes-Related Conditions and Prevents Ischemic Damage in Mouse Retinal Capillaries.Investigative ophthalmology & visual science · 2025Article
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- Ascorbic acid mitigates the impact of oxidative stress in a human model of febrile seizure and mesial temporal lobe epilepsy.Scientific reports · 2024Article
- Peptain-1 blocks ischemia/reperfusion-induced retinal capillary degeneration in mice.Frontiers in cellular neuroscience · 2024Article
- The role of heat shock proteins in the pathogenesis of heart failure (Review).International journal of molecular medicine · 2023Review
- The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death.International journal of molecular sciences · 2023Article
- Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective.International journal of molecular sciences · 2023Review
- Impact of Non-Invasive Physical Plasma on Heat Shock Protein Functionality in Eukaryotic Cells.Biomedicines · 2023Article
- HSP27 modulates tumoural immune evasion by enhancing STAT3-mediated upregulation of PD-L1 and NLRC5 in ovarian cancer.Ecancermedicalscience · 2023Article
- The protective role of HSP27 in ocular diseases.Molecular biology reports · 2022Review
- Identification of the Relationship between Hub Genes and Immune Cell Infiltration in Vascular Endothelial Cells of Proliferative Diabetic Retinopathy Using Bioinformatics Methods.Disease markers · 2022Article
- Small Heat Shock Proteins in Retinal Diseases.Frontiers in molecular biosciences · 2022Review
- Thermal Injury Induces Small Heat Shock Protein in the Optic Nerve Head In Vivo.Korean journal of ophthalmology : KJO · 2021Article
- Damage-Associated Molecular Patterns and Th-Cell-Related Cytokines Released after Progressive Effort.Journal of clinical medicine · 2020Article
- Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament.International journal of molecular sciences · 2020Article
- Endothelial Dysfunction in Diabetic Retinopathy.Frontiers in endocrinology · 2020Review
- Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina.International journal of molecular sciences · 2018Review
- Article
- The Absence of Indoleamine 2,3-Dioxygenase Inhibits Retinal Capillary Degeneration in Diabetic Mice.Investigative ophthalmology & visual science · 2018Article
- Sweet Stress: Coping With Vascular Dysfunction in Diabetic Retinopathy.Frontiers in physiology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The formation of acellular capillaries in the retina, a hallmark feature of diabetic retinopathy, is caused by apoptosis of endothelial cells and pericytes. The biochemical mechanism of such apoptosis remains unclear. Small heat shock proteins play an important role in the regulation of apoptosis. In the diabetic retina, pro-inflammatory cytokines are upregulated. In this study, we investigated the effects of pro-inflammatory cytokines on small heat shock protein 27 (Hsp27) in human retinal endothelial cells (HREC). In HREC cultured in the presence of cytokine mixtures (CM), a significant downregulation of Hsp27 at the protein and mRNA level occurred, with no effect on HSF-1, the transcription factor for Hsp27. The presence of high glucose (25mM) amplified the effects of cytokines on Hsp27. CM activated indoleamine 2,3-dioxygenase (IDO) and enhanced the production of kynurenine and ROS. An inhibitor of IDO, 1-methyl tryptophan (MT), inhibited the effects of CM on Hsp27. CM also upregulated NOS2 and, consequently, nitric oxide (NO). A NOS inhibitor, L-NAME, and a ROS scavenger blocked the CM-mediated Hsp27 downregulation. While a NO donor in the culture medium did not decrease the Hsp27 content, a peroxynitrite donor and exogenous peroxynitrite did. The cytokines and high glucose-induced apoptosis of HREC were inhibited by MT and L-NAME. Downregulation of Hsp27 by a siRNA treatment promoted apoptosis in HREC. Together, these data suggest that pro-inflammatory cytokines induce the formation of ROS and NO, which, through the formation of peroxynitrite, reduce the Hsp27 content and bring about apoptosis of retinal capillary endothelial cells.
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