{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:11:24Z","timestamp":1790806284482,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Crohn\u2019s disease (CD) is an incurable chronic intestinal inflammatory disease with no recognized cause. It has been reported that the mechanosensitive ion channel PIEZO1 initiates proinflammatory responses. However, little is known about the role of PIEZO1 in CD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ileum biopsies were obtained from 30 patients with CD and 15 healthy volunteers. Clinical data were collected to determine the relationship between CD and PIEZO1. First, HT29 cells were incubated with Yoda1 and GsMTx4 (Grammostola spatulata mechanotoxin 4) to activate and inhibit PIEZO1, respectively. Second, PIEZO1 knockdown was performed using small interfering RNA. Third, calcium imaging, flow cytometry, and immunofluorescence were used to detect intracellular calcium and mitochondrial function. Last, real-time quantitative polymerase chain reaction, immunoblotting, and enzyme-linked immunosorbent assay were used to quantify PIEZO1, proinflammatory cytokines, and NLRP3 (NOD-like receptor 3)\u2013related compounds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PIEZO1 was highly expressed in the ileum of patients with CD and correlated positively with the Crohn\u2019s Disease Activity Index, platelet count, and hematocrit and fecal calprotectin levels. In HT29 cells, Yoda1 triggered calcium influx, which was inhibited by GsMTx4 treatment and small interfering RNA\u2013mediated PIEZO1 knockdown. Increased calcium concentrations resulted in increased reactive oxygen species accumulation and decreased mitochondrial membrane potential, whereas decreased calcium concentrations caused by GsMTx4 and PIEZO1 knockdown had the opposite effect. Mechanistically, molecules in the NLRP3 pathway were activated in patients with CD and HT29 cells were stimulated by lipopolysaccharide; these effects were reversed by the knockdown of PIEZO1. Finally, PIEZO1 and NLRP3 knockdown decreased proinflammatory cytokine levels in HT29 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PIEZO1 in intestinal epithelial cells caused calcium influx, which resulted in mitochondrial dysfunction and activated the NLRP3 inflammasome, mediating intestinal inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izac152","type":"journal-article","created":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T12:09:34Z","timestamp":1659182974000},"page":"103-115","source":"Crossref","is-referenced-by-count":54,"title":["The Mechanosensitive Ion Channel PIEZO1 in Intestinal Epithelial Cells Mediates Inflammation through the NOD-Like Receptor 3 Pathway in Crohn\u2019s Disease"],"prefix":"10.1093","volume":"29","author":[{"given":"Qiuyuan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University , Hefei , China"},{"name":"Key Laboratory of Digestive Diseases of Anhui Province , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University , Hefei , China"},{"name":"Key Laboratory of Digestive Diseases of Anhui Province , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, First Affiliated Hospital of Anhui Medical University , Hefei , China and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Scientific Research, Anhui Medical University , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University , Hefei , China"},{"name":"Key Laboratory of Digestive Diseases of Anhui Province , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University , Hefei , China"},{"name":"Key Laboratory of Digestive Diseases of Anhui Province , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0635-6564","authenticated-orcid":false,"given":"Qiao","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University , Hefei , China"},{"name":"Key Laboratory of Digestive Diseases of Anhui Province , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"2023010801580692300_CIT0001","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/ecco-jcc\/jjw168","article-title":"3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn\u2019s Disease 2016: Part 1: diagnosis and medical management","volume":"11","author":"Gomoll\u00f3n","year":"2016","journal-title":"J Crohn\u2019s Colitis."},{"key":"2023010801580692300_CIT0002","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1080\/00365521.2020.1780305","article-title":"Ileocolic anastomotic inflammation after resection for Crohn\u2019s disease indicates disease recurrence: a histopathologic study","volume":"55","author":"Hirten","year":"2020","journal-title":"Scand J Gastroenterol."},{"key":"2023010801580692300_CIT0003","doi-asserted-by":"crossref","first-page":"e12990","DOI":"10.1111\/sji.12990","article-title":"Mechanism of fibrosis and stricture formation in Crohn\u2019s disease","volume":"92","author":"Alfredsson","year":"2020","journal-title":"Scand J Immunol."},{"key":"2023010801580692300_CIT0004","doi-asserted-by":"crossref","first-page":"E7632","DOI":"10.1073\/pnas.1804938115","article-title":"A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release","volume":"115","author":"Alcaino","year":"2018","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2023010801580692300_CIT0005","doi-asserted-by":"crossref","first-page":"11566","DOI":"10.3390\/ijms222111566","article-title":"Mechanotransduction at the plasma membrane-cytoskeleton interface","volume":"22","author":"Uray","year":"2021","journal-title":"Int J Mol Sci."},{"key":"2023010801580692300_CIT0006","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nature03896","article-title":"possible unifying principle for mechanosensation","volume":"436","author":"Kung","year":"2005","journal-title":"Nature."},{"key":"2023010801580692300_CIT0007","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science."},{"key":"2023010801580692300_CIT0008","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature25453","article-title":"Structure of the mechanically activated ion channel Piezo1","volume":"554","author":"Saotome","year":"2018","journal-title":"Nature."},{"key":"2023010801580692300_CIT0009","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.cell.2019.08.049","article-title":"Mammalian mechanoelectrical transduction: structure and function of force-gated ion channels","volume":"179","author":"Douguet","year":"2019","journal-title":"Cell."},{"key":"2023010801580692300_CIT0010","first-page":"629","article-title":"Mechanosensitive ion channel Piezo1 promotes prostate cancer development through the activation of the Akt\/mTOR pathway and acceleration of cell cycle","volume":"55","author":"Han","year":"2019","journal-title":"Int J Oncol."},{"key":"2023010801580692300_CIT0011","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1038\/s41467-018-04194-9","article-title":"Piezo1 is a mechanically activated ion channel and mediates pressure induced pancreatitis","volume":"9","author":"Romac","year":"2018","journal-title":"Nat Commun."},{"key":"2023010801580692300_CIT0012","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41467-019-14146-6","article-title":"Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk","volume":"11","author":"Wang","year":"2020","journal-title":"Nat Commun."},{"key":"2023010801580692300_CIT0013","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cell.2018.02.047","article-title":"Common PIEZO1 allele in African populations causes RBC dehydration and attenuates plasmodium infection","volume":"173","author":"Ma","year":"2018","journal-title":"Cell."},{"key":"2023010801580692300_CIT0014","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41586-019-1485-8","article-title":"Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity","volume":"573","author":"Solis","year":"2019","journal-title":"Nature."},{"key":"2023010801580692300_CIT0015","first-page":"744","article-title":"Soluble uric acid induces inflammation via TLR4\/NLRP3 pathway in intestinal epithelial cells","volume":"23","author":"Ma","year":"2020","journal-title":"Iran J Basic Med Sci."},{"key":"2023010801580692300_CIT0016","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fimmu.2019.00276","article-title":"NLRP3 inflammasome and inflammatory bowel disease","volume":"10","author":"Zhen","year":"2019","journal-title":"Front Immunol."},{"key":"2023010801580692300_CIT0017","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/s41419-019-2157-1","article-title":"NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-kappaB signaling","volume":"10","author":"Chen","year":"2019","journal-title":"Cell Death Dis."},{"key":"2023010801580692300_CIT0018","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1136\/gut.2009.197822","article-title":"Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome","volume":"59","author":"Bauer","year":"2010","journal-title":"Gut."},{"key":"2023010801580692300_CIT0019","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.it.2018.01.009","article-title":"Orchestration of NLRP3 inflammasome activation by ion fluxes","volume":"39","author":"Gong","year":"2018","journal-title":"Trends Immunol."},{"key":"2023010801580692300_CIT0020","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1136\/gutjnl-2021-324855","article-title":"Calprotectin: from biomarker to biological function","volume":"70","author":"Jukic","year":"2021","journal-title":"Gut."},{"key":"2023010801580692300_CIT0021","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/nature10812","article-title":"Piezo proteins are pore-forming subunits of mechanically activated channels","volume":"483","author":"Coste","year":"2012","journal-title":"Nature."},{"key":"2023010801580692300_CIT0022","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.bbamcr.2018.10.016","article-title":"Calcium, mitochondria and cell metabolism: a functional triangle in bioenergetics","volume":"1866","author":"Rossi","year":"2019","journal-title":"Biochim Biophys Acta Mol Cell Res."},{"key":"2023010801580692300_CIT0023","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature."},{"key":"2023010801580692300_CIT0024","doi-asserted-by":"crossref","first-page":"eabb5168","DOI":"10.1126\/sciimmunol.abb5168","article-title":"Targeting Piezo1 unleashes innate immunity against cancer and infectious disease","volume":"5","author":"Aykut","year":"2020","journal-title":"Sci Immunol."},{"key":"2023010801580692300_CIT0025","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s13577-021-00600-5","article-title":"Piezo1 mediates endothelial atherogenic inflammatory responses via regulation of YAP\/TAZ activation","volume":"35","author":"Yang","year":"2022","journal-title":"Hum Cell."},{"key":"2023010801580692300_CIT0026","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.neuron.2020.07.025","article-title":"Piezo1-mediated Ca2+ activities regulate brain vascular pathfinding during development","volume":"108","author":"Liu","year":"2020","journal-title":"Neuron."},{"key":"2023010801580692300_CIT0027","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1161\/HYPERTENSIONAHA.121.17177","article-title":"Piezo1-mediated mechanotransduction promotes cardiac hypertrophy by impairing calcium homeostasis to activate calpain\/calcineurin signaling","volume":"78","author":"Zhang","year":"2021","journal-title":"Hypertension."},{"key":"2023010801580692300_CIT0028","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1038\/s41467-020-16026-w","article-title":"Adipocyte Piezo1 mediates obesogenic adipogenesis through the FGF1\/FGFR1 signaling pathway in mice","volume":"11","author":"Wang","year":"2020","journal-title":"Nat Commun."},{"key":"2023010801580692300_CIT0029","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1161\/HYPERTENSIONAHA.120.16629","article-title":"Upregulation of Piezo1 (Piezo type mechanosensitive ion channel component 1) enhances the intracellular free calcium in pulmonary arterial smooth muscle cells from idiopathic pulmonary arterial hypertension patients","volume":"77","author":"Liao","year":"2021","journal-title":"Hypertension."},{"key":"2023010801580692300_CIT0030","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s41418-020-0593-1","article-title":"Urolithin a suppresses high glucose-induced neuronal amyloidogenesis by modulating TGM2-dependent ER-mitochondria contacts and calcium homeostasis","volume":"28","author":"Lee","year":"2021","journal-title":"Cell Death Differ."},{"key":"2023010801580692300_CIT0031","doi-asserted-by":"crossref","first-page":"748758","DOI":"10.3389\/fimmu.2021.748758","article-title":"mtROS induced via TLR-2-SOCE signaling plays proapoptotic and bactericidal role in mycobacterium fortuitum-infected head kidney macrophages of clarias gariepinus","volume":"12","author":"Dahiya","year":"2021","journal-title":"Front Immunol."},{"key":"2023010801580692300_CIT0032","doi-asserted-by":"crossref","first-page":"101381","DOI":"10.1016\/j.redox.2019.101381","article-title":"Acetaldehyde induces phosphorylation of dynamin-related protein 1 and mitochondrial dysfunction via elevating intracellular ROS and Ca2+ levels","volume":"28","author":"Yan","year":"2020","journal-title":"Redox Biol."},{"key":"2023010801580692300_CIT0033","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.3390\/ijms21062109","article-title":"Calcium-dependent calpain activation-mediated mitochondrial dysfunction and oxidative stress are required for cytotoxicity of epinecidin-1 in human synovial sarcoma SW982 cells","volume":"21","author":"Su","year":"2020","journal-title":"Int J Mol Sci."},{"key":"2023010801580692300_CIT0034","doi-asserted-by":"crossref","first-page":"109733","DOI":"10.1016\/j.cellsig.2020.109733","article-title":"Capsaicin induces mitochondrial dysfunction and apoptosis in anaplastic thyroid carcinoma cells via TRPV1-mediated mitochondrial calcium overload","volume":"75","author":"Xu","year":"2020","journal-title":"Cell Signal."},{"key":"2023010801580692300_CIT0035","doi-asserted-by":"crossref","first-page":"106681","DOI":"10.1016\/j.intimp.2020.106681","article-title":"Piezo1 activates the NLRP3 inflammasome in nucleus pulposus cell-mediated by Ca2+\/NF-\u03baB pathway","volume":"85","author":"Sun","year":"2020","journal-title":"Int Immunopharmacol."},{"key":"2023010801580692300_CIT0036","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/cmi.2015.95","article-title":"Molecular mechanisms regulating NLRP3 inflammasome activation","volume":"13","author":"Jo","year":"2016","journal-title":"Cell Mol Immunol."},{"key":"2023010801580692300_CIT0037","doi-asserted-by":"crossref","first-page":"100889","DOI":"10.1016\/j.mam.2020.100889","article-title":"The NLRP3 inflammasome: mechanism of action, role in disease and therapies","volume":"76","author":"Wang","year":"2020","journal-title":"Mol Aspects Med."},{"key":"2023010801580692300_CIT0038","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.neuroscience.2020.08.004","article-title":"NLRP3 inflammasomes in Parkinson\u2019s disease and their regulation by Parkin","volume":"446","author":"Yan","year":"2020","journal-title":"Neuroscience."},{"key":"2023010801580692300_CIT0039","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s00018-022-04155-y","article-title":"Thioredoxin reductase 3 suppression promotes colitis and carcinogenesis via activating pyroptosis and necrosis","volume":"79","author":"Liu","year":"2022","journal-title":"Cell Mol Life Sci."}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/advance-article-pdf\/doi\/10.1093\/ibd\/izac152\/45195138\/izac152.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/29\/1\/103\/48342971\/izac152.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/29\/1\/103\/48342971\/izac152.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T20:59:13Z","timestamp":1673125153000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/29\/1\/103\/6652368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,30]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,7,30]]},"published-print":{"date-parts":[[2023,1,5]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izac152","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2022,7,30]]}}}