ArticleThe Journal of clinical investigation2020
TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 192 citations in OpenAlex.
- Piezo1 in digestive homeostasis and disease: Barrier function, immune signalling, cellular injury and metabolism.Clinical and translational medicine · 2026Review
- Piezo ion channels in the digestive system: Mechanotransduction pathways and therapeutic targeting strategies.Genes & diseases · 2026Review
- Transforming destructive mechanical cues into therapeutic power: Activation of PIEZO1 and TRPV4 counteracts mechano-induced damage of cellular junctions in Hailey-Hailey disease.Journal of advanced research · 2026Article
- Autophagy dysfunction in pancreatic acinar cells in acute pancreatitis: from molecular mechinery and trypsinogen activation to heterogeneity and therapeutic implications.Journal of molecular histology · 2026Review
- The Role of Piezo Ion Channels in Pulmonary Hypertension.Pulmonary circulation · 2026Review
- NF-κB-Dependent Transcriptional Regulation of Piezo1 Mediates Bacterial Clearance on Infected Lung Stiffness.American journal of respiratory cell and molecular biology · 2026Article
- Intraductal digestive enzyme accumulation drives lethal hemorrhagic necrotizing pancreatitis and enables therapeutic intervention.Research square · 2026Article
- Article
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- The Mechanosensation-Metabolism-Inflammation Axis: The Central Role of Piezo1 and TRPV4 in Hypertension-Related Atherosclerosis.International journal of general medicine · 2026Review
- The role of Piezo1 in immune cells and pregnancy.Frontiers in immunology · 2026Review
- The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression.Frontiers in immunology · 2026Review
- Myometrial mechanotransduction and the timing of parturition: ion-channel pathways linking uterine stretch, calcium signaling, and inflammation.Frontiers in physiology · 2026Review
- Role of TRP channels in lymphatic function.Frontiers in physiology · 2026Review
- PIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Stochastic Nature of Fascia: From Layered Pedagogical Artifact to Morphogenetic Reality in Clinical Anatomy.Life (Basel, Switzerland) · 2025Article
- How do mechanical forces impact macrophages in the processes of mechanosensing and mechanotransduction?Journal of Zhejiang University. Science. B · 2025Review
- Loss of TRPV4 reduces pancreatic cancer growth and metastasis.JCI insight · 2025Article
- Piezo knockdown reduces 5‑hydroxytryptamine release from enterochromaffin cells and exacerbates intestinal dyskinesia in mice with functional constipation.International journal of molecular medicine · 2025Article
- NF-κB-Dependent Transcriptional Regulation of Piezo1 Mediates Bacterial Clearance on Stiffened Lung Matrix.bioRxiv : the preprint server for biology · 2025Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Elevated pressure in the pancreatic gland is the central cause of pancreatitis following abdominal trauma, surgery, endoscopic retrograde cholangiopancreatography, and gallstones. In the pancreas, excessive intracellular calcium causes mitochondrial dysfunction, premature zymogen activation, and necrosis, ultimately leading to pancreatitis. Although stimulation of the mechanically activated, calcium-permeable ion channel Piezo1 in the pancreatic acinar cell is the initial step in pressure-induced pancreatitis, activation of Piezo1 produces only transient elevation in intracellular calcium that is insufficient to cause pancreatitis. Therefore, how pressure produces a prolonged calcium elevation necessary to induce pancreatitis is unknown. We demonstrate that Piezo1 activation in pancreatic acinar cells caused a prolonged elevation in intracellular calcium levels, mitochondrial depolarization, intracellular trypsin activation, and cell death. Notably, these effects were dependent on the degree and duration of force applied to the cell. Low or transient force was insufficient to activate these pathological changes, whereas higher and prolonged application of force triggered sustained elevation in intracellular calcium, leading to enzyme activation and cell death. All of these pathological events were rescued in acinar cells treated with a Piezo1 antagonist and in acinar cells from mice with genetic deletion of Piezo1. We discovered that Piezo1 stimulation triggered transient receptor potential vanilloid subfamily 4 (TRPV4) channel opening, which was responsible for the sustained elevation in intracellular calcium that caused intracellular organelle dysfunction. Moreover, TRPV4 gene-KO mice were protected from Piezo1 agonist- and pressure-induced pancreatitis. These studies unveil a calcium signaling pathway in which a Piezo1-induced TRPV4 channel opening causes pancreatitis.
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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.