ArticleJCI insight2019
Piezo1 incorporates mechanical force signals into the genetic program that governs lymphatic valve development and maintenance.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
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Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Role of meningeal lymphatic vessels in brain homeostasis.Frontiers in immunology · 2025Pooled it
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Piezo channels in physical field therapy: From mechanotransduction mechanisms to bioelectromagnetic modulation and biomedical applications.Mechanobiology in medicine · 2026Review
- Piezo1 channel: structure, mechanogating mechanism, functions, diseases and therapeutic strategy.Molecular biomedicine · 2026Review
- CXCL12/CXCR4 Governs Lymphatic Valve Formation Through Flow Dependent AKT/FOXO1/FOXC2 Activation.bioRxiv : the preprint server for biology · 2026Article
- Mechanoreceptor plexin D1 regulates lymphatic valve morphogenesis and lymphedema pathogenesis.The Journal of clinical investigation · 2026Article
- Functional characterization and classification of mechanosensitive bladder afferents.bioRxiv : the preprint server for biology · 2026Article
- Yoda molecules agonize PIEZO2.bioRxiv : the preprint server for biology · 2026Article
- Pacemaking in the lymphatic system.The Journal of physiology · 2026Review
- The Glymphatic System and Meningeal Lymphatics: Current Understandings and Future Perspectives.MedComm · 2026Review
- Lysophosphatidic acid-mediated NF-κB activation promotes FOXC2 expression essential for lymphatic valve development.The Journal of clinical investigation · 2026Article
- Targeting Piezo1/2 ion channels for modulation of the lymphatic system: mechanisms, applications, and therapeutic prospects.Burns & trauma · 2026Review
- The Dual Role of Piezo1 in Cancer: Mechanotransduction, Microenvironment Remodelling, and Therapeutic Opportunities.Drug design, development and therapy · 2026Review
- A guide to cell-type-specific Cre mouse models in atherosclerosis: from background strains to future directions.Frontiers in cardiovascular medicine · 2026Review
- CaAmerican journal of physiology. Cell physiology · 2025Article
- 3D imaging and single-cell analysis reveal cellular heterogeneity of lymphatic valve endothelial cell types.iScience · 2025Article
- Perceiving traumatic brain injury from glymphatic system.Molecular psychiatry · 2025Review
- PIEZO Force Sensing in Vascular Biology: An Explosion of New Knowledge, Concepts and Opportunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Roles of G-protein coupled receptors and mechanosensitive ion channels in pressure-induced chronotropy of lymphatic vessels.bioRxiv : the preprint server for biology · 2025Article
- S1PR1 regulates lymphatic valve development and tertiary lymphoid organ formation in the ileum.The Journal of experimental medicine · 2025Article
37 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
20 authors at 6 institutions in 2 countries.
Funding
Abstract
The lymphatic system plays crucial roles in tissue homeostasis, lipid absorption, and immune cell trafficking. Although lymphatic valves ensure unidirectional lymph flows, the flow itself controls lymphatic valve formation. Here, we demonstrate that a mechanically activated ion channel Piezo1 senses oscillating shear stress (OSS) and incorporates the signal into the genetic program controlling lymphatic valve development and maintenance. Time-controlled deletion of Piezo1 using a pan-endothelial Cre driver (Cdh5[PAC]-CreERT2) or lymphatic-specific Cre driver (Prox1-CreERT2) equally inhibited lymphatic valve formation in newborn mice. Furthermore, Piezo1 deletion in adult lymphatics caused substantial lymphatic valve degeneration. Piezo1 knockdown in cultured lymphatic endothelial cells (LECs) largely abrogated the OSS-induced upregulation of the lymphatic valve signature genes. Conversely, ectopic Piezo1 overexpression upregulated the lymphatic valve genes in the absence of OSS. Remarkably, activation of Piezo1 using chemical agonist Yoda1 not only accelerated lymphatic valve formation in animals, but also triggered upregulation of some lymphatic valve genes in cultured LECs without exposure to OSS. In summary, our studies together demonstrate that Piezo1 is the force sensor in the mechanotransduction pathway controlling lymphatic valve development and maintenance, and Piezo1 activation is a potentially novel therapeutic strategy for congenital and surgery-associated lymphedema.
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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.