ArticleJournal of inflammation (London, England)2015
ATF4 is a novel regulator of MCP-1 in microvascular endothelial cells.
Article in Journal of inflammation (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Spatial transcriptomics reveals regionally altered gene expression that drives retinal degeneration.Communications biology · 2025Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Renoprotective effect ofIranian journal of basic medical sciences · 2024Article
- L-Proline Prevents Endoplasmic Reticulum Stress in Microglial Cells Exposed to L-azetidine-2-carboxylic Acid.Molecules (Basel, Switzerland) · 2023Article
- Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.Molecular neurodegeneration · 2022Review
- The Role of CCL2/CCR2 Axis in Cerebral Ischemia-Reperfusion Injury and Treatment: From Animal Experiments to Clinical Trials.International journal of molecular sciences · 2022Review
- The role of lipopolysaccharides in diabetic retinopathy.BMC ophthalmology · 2022Review
- Role of Activating Transcription Factor 4 in Murine Choroidal Neovascularization Model.International journal of molecular sciences · 2021Article
- Review
- Regulation of cellular immunity by activating transcription factor 4.Immunology letters · 2020Review
- A SARS-CoV-2 host infection model network based on genomic human Transcription Factors (TFs) depletion.Heliyon · 2020Article
- MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy.Cardiovascular diabetology · 2020Review
- Metformin/Donepezil combination modulates brain antioxidant status and hippocampal endoplasmic reticulum stress in type 2 diabetic rats.Journal of diabetes and metabolic disorders · 2020Article
- Lineage-Restricted Regulation of SCD and Fatty Acid Saturation by MITF Controls Melanoma Phenotypic Plasticity.Molecular cell · 2020Article
- Black Sorghum Phenolic Extract Regulates Expression of Genes Associated with Oxidative Stress and Inflammation in Human Endothelial Cells.Molecules (Basel, Switzerland) · 2019Article
- RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection.Nature communications · 2019Article
- Loss of XBP1 Leads to Early-Onset Retinal Neurodegeneration in a Mouse Model of Type I Diabetes.Journal of clinical medicine · 2019Article
- Involvement of Orai1 in tunicamycin-induced endothelial dysfunction.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Article
- Loss of X-box binding protein 1 in Müller cells augments retinal inflammation in a mouse model of diabetes.Diabetologia · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMonocyte chemoattractant protein-1 (MCP-1) is a major chemokine that recruits monocyte/macrophage to the site of tissue injury and plays a critical role in microvascular complications of diabetes. However, the mechanisms underlying the regulation of MCP-1 are not fully understood. The present study aims to explore the role of activating transcription factor 4 (ATF4), an ER stress-inducible transcription factor, in regulation of MCP-1 expression and production in brain and retinal microvascular endothelial cells.
methodsFor in vitro study, primary brain microvascular endothelial cells isolated from ATF4 knockout mice or mouse retinal endothelial cells were treated with lipopolysaccharide (LPS) to induce MCP-1 expression. ATF4 expression/function was manipulated by adenoviruses expressing wild type ATF4 (Ad-ATF4) or a dominant negative mutant of the protein (Ad-ATF4DN). For in vivo study, MCP-1 expression was induced by intravitreal injection of LPS or Ad-ATF4 in heterozygous ATF4 knockout or wild type mice.
resultsLPS treatment induced a dose- and time-dependent increase in ATF4 expression, ER stress and MCP-1 production in brain and retinal microvascular endothelial cells. Overexpression of ATF4 in endothelial cells significantly increased the secretion of MCP-1 and promoted THP-1 monocyte-endothelial cell adhesion. Conditioned medium from ATF4-overexpressiing endothelial cells significantly enhanced THP-1 cell migration. Consistently, intravitreal injection of Ad-ATF4 remarkably enhanced retinal levels of MCP-1 and promoted inflammatory cell infiltration into the vitreous and retina. In contrast, LPS-induced MCP-1 upregulation was markedly attenuated in ATF4-deficient endothelial cells and in retinas of ATF4 knockout mice, suggesting that ATF4 is essential for LPS-induced MCP-1 production in endothelial cells and in the retina. Mechanistically, overexpression of ATF4 enhanced, while inhibition of ATF4, attenuated the basal and LPS-stimulated phosphorylation of NF-κB, P38, and JNK. Furthermore, pharmacological inhibition of NF-κB, P38, or JNK significantly reduced ATF4-stimulated MCP-1 secretion from endothelial cells.
conclusionsTaken together, our results suggest a critical role of ATF4 in the regulation of MCP-1 production in retinal and brain microvascular endothelial cells, which may contribute to inflammation-related endothelial injury in diseases such as diabetic retinopathy.
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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.