ArticleThe Journal of biological chemistry2014
Endothelial Kruppel-like factor 4 regulates angiogenesis and the Notch signaling pathway.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- MicroRNAs in Tumor Endothelial Cells: Regulation, Function and Therapeutic Applications.Cells · 2023Pooled it
- Multi-species meta-analysis identifies transcriptional signatures associated with cardiac endothelial responses in the ischaemic heart.Cardiovascular research · 2023Pooled it
- HIV vasculopathy: role of mononuclear cell-associated Krüppel-like factors 2 and 4.AIDS (London, England) · 2015Trial
- Reduced KLF4 expression in endothelial cells triggers pulmonary vascular abnormalities associated with experimental congenital diaphragmatic hernia.Cellular and molecular life sciences : CMLS · 2026Article
- Ethanol Alters DNMT1/3a/3b Expression Profile, Promotes Persistent DNA Hypomethylation in Human Brain Endothelial Cells and Impairs Late Cortical Angiogenesis.Journal of neurochemistry · 2026Article
- Review
- Post-translational modification of transcription factors: perspectives in vascular medicine.Cell death & disease · 2025Review
- Krüppel-like factor 4 transcription factor in blood-brain barrier endothelial cells: A potential role in Alzheimer's disease.Animal models and experimental medicine · 2025Review
- Origin and stepwise evolution of vertebrate lungs.Nature ecology & evolution · 2025Article
- Endothelial Dysfunction in Atherosclerosis: Experimental Models and Therapeutics.Biomaterials research · 2025Review
- Unraveling the Molecular Mechanisms of SIRT7 in Angiogenesis: Insights from Substrate Clues.International journal of molecular sciences · 2024Review
- Discovery of Transcription Factors Involved in the Maintenance of Resident Vascular Endothelial Stem Cell Properties.Molecular and cellular biology · 2024Article
- Micro-Executor of Natural Products in Metabolic Diseases.Molecules (Basel, Switzerland) · 2023Review
- Krüppel-like factor 10 modulates stem cell phenotypes of pancreatic adenocarcinoma by transcriptionally regulating notch receptors.Journal of biomedical science · 2023Article
- KLF4 transcription factor in tumorigenesis.Cell death discovery · 2023Review
- Krüppel-like factors in tumors: Key regulators and therapeutic avenues.Frontiers in oncology · 2023Review
- microRNA-130b May Induce Cerebral Vasospasm after Subarachnoid Hemorrhage via Modulating Kruppel-like Factor 4.Molecular and cellular biology · 2023Article
- Remarkable sex-specific differences at single-cell resolution in neonatal hyperoxic lung injury.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Evaluation of the Feasibility of Endothelial Colony-Forming Cells to Develop Tissue-Engineered Vascular Grafts Based on the Gene Expression Profile Analysis.Sovremennye tekhnologii v meditsine · 2022Article
- Micro-RNA 92a as a Therapeutic Target for Cardiac Microvascular Dysfunction in Diabetes.Biomedicines · 2021Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Regulation of endothelial cell biology by the Notch signaling pathway (Notch) is essential to vascular development, homeostasis, and sprouting angiogenesis. Although Notch determines cell fate and differentiation in a wide variety of cells, the molecular basis of upstream regulation of Notch remains poorly understood. Our group and others have implicated the Krüppel-like factor family of transcription factors as critical regulators of endothelial function. Here, we show that Krüppel-like factor 4 (KLF4) is a central regulator of sprouting angiogenesis via regulating Notch. Using a murine model in which KLF4 is overexpressed exclusively in the endothelium, we found that sustained expression of KLF4 promotes ineffective angiogenesis leading to diminished tumor growth independent of endothelial cell proliferation or cell cycling effects. These tumors feature increased vessel density yet are hypoperfused, leading to tumor hypoxia. Mechanistically, we show that KLF4 differentially regulates expression of Notch receptors, ligands, and target genes. We also demonstrate that KLF4 limits cleavage-mediated activation of Notch1. Finally, we rescue Notch target gene expression and the KLF4 sprouting angiogenesis phenotype by supplementation of DLL4 recombinant protein. Identification of this hitherto undiscovered role of KLF4 implicates this transcription factor as a critical regulator of Notch, tumor angiogenesis, and sprouting angiogenesis.
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Registered trials
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.