ArticlePurinergic signalling2015
Shear stress modulates endothelial KLF2 through activation of P2X4.
Article in Purinergic signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
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- Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries.Life (Basel, Switzerland) · 2025Article
- Biophysical and Biochemical Roles of Shear Stress on Endothelium: A Revisit and New Insights.Circulation research · 2025Review
- Krüppel-like factor 2 is an endoprotective transcription factor in diabetic kidney disease.American journal of physiology. Cell physiology · 2024Review
- Purinoceptor: a novel target for hypertension.Purinergic signalling · 2023Review
- Purinergic receptors mediate endothelial dysfunction and participate in atherosclerosis.Purinergic signalling · 2023Review
- The Interplay of Endothelial P2Y Receptors in Cardiovascular Health: From Vascular Physiology to Pathology.International journal of molecular sciences · 2022Review
- Role of the Purinergic P2Y2 Receptor in Pulmonary Hypertension.International journal of environmental research and public health · 2021Review
- Exosomes in Atherosclerosis, a Double-Edged Sword: Their Role in Disease Pathogenesis and Their Potential as Novel Therapeutics.The AAPS journal · 2021Review
- Phenotypic diversity and metabolic specialization of renal endothelial cells.Nature reviews. Nephrology · 2021Review
- Metabolic adaptations of cells at the vascular-immune interface during atherosclerosis.Molecular aspects of medicine · 2021Article
- Purinergic Regulation of Endothelial Barrier Function.International journal of molecular sciences · 2021Review
- ZNF354C is a transcriptional repressor that inhibits endothelial angiogenic sprouting.Scientific reports · 2020Article
- Resolving the Ionotropic P2X4 Receptor Mystery Points Towards a New Therapeutic Target for Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Biomechanical Cues Direct Valvulogenesis.Journal of cardiovascular development and disease · 2020Review
- Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease.Antioxidants & redox signaling · 2019Review
- Effects of silibinin on hepatic warm ischemia-reperfusion injury in the rat model.Iranian journal of basic medical sciences · 2019Article
- A GBF1-Dependent Mechanism for Environmentally Responsive Regulation of ER-Golgi Transport.Developmental cell · 2019Article
- Hydrodynamic shear stress promotes epithelial-mesenchymal transition by downregulating ERK and GSK3β activities.Breast cancer research : BCR · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial cells that are in direct contact with blood flow are exposed to fluid shear stress and regulate vascular homeostasis. Studies report endothelial cells to release ATP in response to shear stress that in turn modulates cellular functions via P2 receptors with P2X4 mediating shear stress-induced calcium signaling and vasodilation. A recent study shows that a loss-of-function polymorphism in the human P2X4 resulting in a Tyr315>Cys variant is associated with increased pulse pressure and impaired endothelial vasodilation. Although the importance of shear stress-induced Krüppel-like factor 2 (KLF2) expression in atheroprotection is well studied, whether ATP regulates KLF2 remains unanswered and is the objective of this study. Using an in vitro model, we show that in human umbilical vein endothelial cells (HUVECs), apyrase decreased shear stress-induced KLF2, KLF4, and NOS3 expression but not that of NFE2L2. Exposure of HUVECs either to shear stress or ATPγS under static conditions increased KLF2 in a P2X4-dependent manner as was evident with both the receptor antagonist and siRNA knockdown. Furthermore, transient transfection of static cultures of human endothelial cells with the Tyr315>Cys mutant P2X4 construct blocked ATP-induced KLF2 expression. Also, P2X4 mediated the shear stress-induced phosphorylation of extracellular regulated kinase-5, a known regulator of KLF2. This study demonstrates a major physiological finding that the shear-induced effects on endothelial KLF2 axis are in part dependent on ATP release and P2X4, a previously unidentified mechanism.
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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.