ArticleThe Journal of biological chemistry2015
EPHB4 Protein Expression in Vascular Smooth Muscle Cells Regulates Their Contractility, and EPHB4 Deletion Leads to Hypotension in Mice.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Analysis of the association of EPHB6, EFNB1 and EFNB3 variants with hypertension risks in males with hypogonadism.Scientific reports · 2018Trial
- Exploring EPHB4 in gait disorders: VUS detection and phenotypic characterization in a toe-walking cohort.Global medical genetics · 2026Article
- EphB4/EphrinB2 signaling regulates pericyte-like function of DPSCs in angiogenesis via transcriptional factor SRF.Stem cell research & therapy · 2026Article
- Forebrain-specific loss of erythropoietin provokes compensatory upregulation of different EPO receptors.Molecular psychiatry · 2026Article
- Identification of Ephrin type-B receptor 4 as a critical mediator of tissue fibrosis.JCI insight · 2025Article
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 2024Review
- Eph-ephrin signaling couples endothelial cell sorting and arterial specification.Nature communications · 2024Article
- Genetic architecture of cardiac dynamic flow volumes.Nature genetics · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Gastrodin attenuates angiotensin II-induced vascular contraction and MLCK/p-MLCPharmaceutical biology · 2023Article
- Identification of Sex-Specific Genetic Polymorphisms Associated with Asthma in Middle-Aged and Older Canadian Adults: An Analysis of CLSA Data.Journal of asthma and allergy · 2023Article
- Angiogenesis depends upon EPHB4-mediated export of collagen IV from vascular endothelial cells.JCI insight · 2022Article
- Activation of EphrinB2 Signaling Promotes Adaptive Venous Remodeling in Murine Arteriovenous Fistulae.The Journal of surgical research · 2021Article
- Multi-trait transcriptome-wide association studies with probabilistic Mendelian randomization.American journal of human genetics · 2021Article
- The Pyrazolo[3,4-Molecules (Basel, Switzerland) · 2020Article
- NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype.PLoS biology · 2020Article
- The receptor tyrosine kinase EPHB6 regulates catecholamine exocytosis in adrenal gland chromaffin cells.The Journal of biological chemistry · 2020Article
- EphB4 signaling maintains the contractile phenotype of adult venous smooth muscle cells.American journal of translational research · 2020Article
- A Variant in the Nicotinic Acetylcholine Receptor Alpha 3 Subunit Gene Is Associated With Hypertension Risks in Hypogonadic Patients.Frontiers in genetics · 2020Article
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Authors and funding
9 authors.
Funding
Abstract
EPH kinases are the largest family of receptor tyrosine kinases, and their ligands, ephrins (EFNs), are also cell surface molecules. This work presents evidence that EPHB4 on vascular smooth muscle cells (VSMCs) is involved in blood pressure regulation. We generated gene KO mice with smooth muscle cell-specific deletion of EPHB4. Male KO mice, but not female KO mice, were hypotensive. VSMCs from male KO mice showed reduced contractility when compared with their WT counterparts. Signaling both from EFNBs to EPHB4 (forward signaling) and from EPHB4 to EFNB2 (reverse signaling) modulated VSMC contractility. At the molecular level, the absence of EPHB4 in VSMCs resulted in compromised signaling from Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) to myosin light chain kinase (MLCK) to myosin light chain, the last of which controls the contraction force of motor molecule myosin. Near the cell membrane, an adaptor protein GRIP1, which can associate with EFNB2, was found to be essential in mediating EPHB4-to-EFNB reverse signaling, which regulated VSMC contractility, based on siRNA gene knockdown studies. Our research indicates that EPHB4 plays an essential role in regulating small artery contractility and blood pressure.
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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.