ArticleThe Journal of biological chemistry2010
Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4).
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Multi-species meta-analysis identifies transcriptional signatures associated with cardiac endothelial responses in the ischaemic heart.Cardiovascular research · 2023Pooled it
- miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition: Therapeutic Implications in Kawasaki Disease.Circulation research · 2017Trial
- Palbociclib targets β-catenin for degradation and synergizes with KRAS or ERK5 inhibition in colorectal cancer preclinical models.Journal of translational medicine · 2026Article
- Mitogen-activated Protein Kinase big Mitogen-activated Kinase-1 Mediates Protection in Liver Ischemia/Reperfusion Injury.Transplantation · 2026Article
- AXL is a novel ERK5/KLF4 target in MEK inhibitor-treated melanoma.Neoplasia (New York, N.Y.) · 2026Article
- The Potential Role of Endothelial Cells in the Pathophysiology, Diagnosis, and Management of Acute Kawasaki Disease.CJC open · 2026Review
- KLF4 overexpression protects against complementmediated endothelial injury in transplant-associated thrombotic microangiopathy.Haematologica · 2026Article
- Statins as Modulators of Epithelial to Mesenchymal Transition in Cardiovascular-Kidney-Metabolic Syndrome: a Comprehensive Review of Mechanisms and Therapeutic Implications.Current atherosclerosis reports · 2025Review
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations.Circulation · 2025Article
- TNIK-driven regulation of ERK5 transcriptional activity in endothelial cells.Frontiers in cardiovascular medicine · 2025Article
- The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood-brain barrier protection.Molecular medicine (Cambridge, Mass.) · 2024Review
- Statins in Mitigating Anticancer Treatment-Related Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.Acta pharmacologica Sinica · 2024Review
- A Potential Role for MAGI-1 in the Bi-Directional Relationship Between Major Depressive Disorder and Cardiovascular Disease.Current atherosclerosis reports · 2024Review
- Bone and Extracellular Signal-Related Kinase 5 (ERK5).Biomolecules · 2024Review
- Article
- HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells.Circulation · 2024Article
- Single-nucleus multiregion transcriptomic analysis of brain vasculature in Alzheimer's disease.Nature neuroscience · 2023Article
- Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MEK5/Erk5 MAPK cascade has recently been implicated in the regulation of endothelial integrity and represents a candidate pathway mediating the beneficial effects of laminar flow, a major factor preventing vascular dysfunction and disease. Here we expressed a constitutively active mutant of MEK5 (MEK5D) to study the transcriptional and functional responses to Erk5 activation in human primary endothelial cells. We provide evidence that constitutive Erk5 activation elicits an overall protective phenotype characterized by increased apoptosis resistance and a decreased angiogenic, migratory, and inflammatory potential. This is supported by bioinformatic microarray analysis, which uncovered a statistical overrepresentation of corresponding functional clusters as well as a significant induction of anti-thrombotic, hemostatic, and vasodilatory genes. We identify KLF4 as a novel Erk5 target and demonstrate a critical role of this transcription factor downstream of Erk5. We show that KLF4 expression largely reproduces the protective phenotype in endothelial cells, whereas KLF4 siRNA suppresses expression of various Erk5 targets. Additionally, we show that vasoprotective statins potently induce KLF4 and KLF4-dependent gene expression via activation of Erk5. Our data underscore a major protective function of the MEK5/Erk5/KLF4 module in ECs and implicate agonistic Erk5 activation as potential strategy for treatment of vascular diseases.
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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.