ArticleScientific reports2017
KDM4B histone demethylase and G9a regulate expression of vascular adhesion proteins in cerebral microvessels.
Article in Scientific reports, 2017. 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, 33 citations in OpenAlex.
- Histone methyltransferase G9a drives vascular smooth muscle cell proliferation and intimal hyperplasia in mice.Acta pharmacologica Sinica · 2026Article
- Inhibition of Astrocytic JMJD3 Attenuates Neuroinflammation-Mediated Blood-Brain Barrier Disruption and Improves Functional Recovery After Intracerebral Hemorrhage in Mice.Brain sciences · 2026Article
- Targeting epigenetic remodeling of the blood-brain barrier: current knowledge for drug therapy.Epigenomics · 2026Review
- Histone demethylases in autophagy and inflammation.Cell communication and signaling : CCS · 2025Review
- Causal associations and shared genetic etiology of neurodegenerative diseases with epigenetic aging and human longevity.Aging cell · 2024Article
- DOT1-like histone lysine methyltransferase is critical for adult vessel maintenance and functions.Animal bioscience · 2024Article
- Age-Related Alterations in Immune Function and Inflammation: Focus on Ischemic Stroke.Aging and disease · 2024Review
- Epigenetic targets to enhance antitumor immune response through the induction of tertiary lymphoid structures.Frontiers in immunology · 2024Review
- Human Macrophage Long Intergenic Noncoding RNA,Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Oleracone F Alleviates Cognitive Impairment and Neuropathology in APPswe/PSEN1dE9 Mice by Reducing the Expression of Vascular Cell Adhesion Molecule and Leukocyte Adhesion to Brain Vascular Endothelial Cells.International journal of molecular sciences · 2023Article
- Article
- Minor Changes for a Major Impact: A Review of Epigenetic Modifications in Cell-Based Therapies for Stroke.International journal of molecular sciences · 2022Review
- The progress of research on histone methylation in ischemic stroke pathogenesis.Journal of physiology and biochemistry · 2022Review
- Microvascular Inflammation and Cardiovascular Prevention: The Role of Microcirculation as Earlier Determinant of Cardiovascular Risk.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2022Review
- KDM4 Involvement in Breast Cancer and Possible Therapeutic Approaches.Frontiers in oncology · 2021Review
- Genetic Aspects of Inflammation and Immune Response in Stroke.International journal of molecular sciences · 2020Review
- Telmisartan Inhibits TNFα-Induced Leukocyte Adhesion by Blocking ICAM-1 Expression in Astroglial Cells but Not in Endothelial Cells.Biomolecules & therapeutics · 2020Article
- Histone methylation and vascular biology.Clinical epigenetics · 2020Review
- Involvement of Epigenetic Mechanisms and Non-coding RNAs in Blood-Brain Barrier and Neurovascular Unit Injury and Recovery After Stroke.Frontiers in neuroscience · 2019Review
- Cell‑specific histone modifications in atherosclerosis (Review).Molecular medicine reports · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression. Inhibition of G9a and EZH2, histone methyltransferases responsible for methylation at H3K9 and H3K27, respectively as well as G9a overexpression demonstrated the involvement of G9a in TNF-α-induced ICAM1 expression and leukocyte adhesion and transmigration. A specific role for KDM4B, a histone demethylase targeting H3K9me2, in TNF-α-induced ICAM1 upregulation was validated with siRNA. Moreover, treating mice with a KDM4 inhibitor ML324 blocked TNF-α-mediated neutrophil adhesion. Similarly, TNF-α-induced VCAM1 expression was suppressed by G9a overexpression and KDM4B knockdown. Collectively, we demonstrated that modification of H3K9me2 by G9a and KDM4B regulates expression of vascular adhesion molecules, and that depletion of these proteins or KDM4B reduces inflammation-induced leukocyte extravasation. Thus, blocking ICAM1 or KDM4B could offer a novel therapeutic opportunity treating brain diseases.
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