ArticleJCI insight2022
Piezo1-mediated stellate cell activation causes pressure-induced pancreatic fibrosis in mice.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 61 citations in OpenAlex.
- Recursive feedback between Piezo1 conformation and membrane mechanics drives self-organization into finite clusters.bioRxiv : the preprint server for biology · 2026Article
- Piezo1 in digestive homeostasis and disease: Barrier function, immune signalling, cellular injury and metabolism.Clinical and translational medicine · 2026Review
- Mechanical stress promotes excessive NETs and exacerbates acute lung injury via Piezo1-mediated mitochondrial dysfunction.Redox biology · 2026Article
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- Discovery of non-opioid peptides that selectively relieve mechanical pain in rodents through inhibition of TRPV4 channels.Acta pharmacologica Sinica · 2026Article
- pH-Dependent Microenvironmental Ionic Signaling in Pancreatic Ductal Adenocarcinoma.Acta physiologica (Oxford, England) · 2026Review
- Mechanistic insights into pancreatic duct pressure: from basic physiology to translational implications.Current opinion in gastroenterology · 2026Review
- Urothelial Piezo1 channel contributes to BOO-induced inflammation, EMT, and bladder fibrosis via activation of NLRP3 inflammasome.Journal of translational medicine · 2026Article
- Platelet-Rich Plasma (PRP) bidirectionally modulates scar formation via the Piezo1-YAP/TAZ axis: a novel mechanotransduction hypothesis.Frontiers in cell and developmental biology · 2026Article
- The role of Piezo1 in immune cells and pregnancy.Frontiers in immunology · 2026Review
- Piezo1 as a mechanical checkpoint in T cell immunotherapy for solid tumors.Frontiers in pharmacology · 2026Review
- Loss of TRPV4 reduces pancreatic cancer growth and metastasis.JCI insight · 2025Article
- Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels.Journal of cell science · 2025Article
- Uniform and controllable surface nano-structure on polyetheretherketone implants can regulate mechanical property to enhance soft tissue integration through Piezo1/TGF-β1 signaling axis.Materials today. Bio · 2025Article
- A synthetic peptide, derived from neurotoxin GsMTx4, acts as a non-opioid analgesic to alleviate mechanical and neuropathic pain through the TRPV4 channel.Acta pharmaceutica Sinica. B · 2025Article
- Shear-Stress Initiates Signal Two of NLRP3 Inflammasome Activation in LPS-Primed Macrophages through Piezo1.ACS applied materials & interfaces · 2025Article
- KPflugers Archiv : European journal of physiology · 2025Article
- Piezo1 and tissue fibrosis: insights into its role and potential for modulation.Burns & trauma · 2025Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic fibrosis is a complication of chronic pancreatitis and is a prominent feature of pancreatic cancer. Pancreatic fibrosis is commonly observed in patients with prolonged pancreatic duct obstruction, which elevates intrapancreatic pressure. We show here that increased pancreatic duct pressure causes fibrosis and describes the mechanism by which pressure increases deposition of extracellular matrix proteins and fibrosis. We found that pancreatic stellate cells (PSCs), the source of the extracellular matrix proteins in fibrosis, express the mechanically activated ion channel Piezo1. By increasing intracellular calcium, mechanical stress or the Piezo1 agonist Yoda1-activated PSCs manifest by loss of perinuclear fat droplets and increased TGF-β1, fibronectin, and type I collagen expression. These effects were blocked by the Piezo1 inhibitor GsMTx4 and absent in PSCs from mice with conditional genetic deletion of Piezo1 in stellate cells, as was pancreatic duct ligation-induced fibrosis. Although TRPV4 has been proposed to have direct mechanosensing properties, we discovered that PSCs from Trpv4-KO mice were protected against Yoda1-triggered activation. Moreover, mice devoid of TRPV4 were protected from pancreatic duct ligation-induced fibrosis. Thus, high pressure within the pancreas stimulates Piezo1 channel opening, and subsequent activation of TRPV4 leads to stellate cell activation and pressure-induced chronic pancreatitis and fibrosis.
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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.