{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:16:29Z","timestamp":1793121389209,"version":"4.5.0"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 DK124474,R01 DK120555"],"award-info":[{"award-number":["R01 DK124474,R01 DK120555"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,22]]},"abstract":"<jats:p>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-\u03b21, 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\u2013induced 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\u2013induced 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.<\/jats:p>","DOI":"10.1172\/jci.insight.158288","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T14:00:46Z","timestamp":1650549646000},"source":"Crossref","is-referenced-by-count":74,"title":["Piezo1-mediated stellate cell activation causes pressure-induced pancreatic fibrosis in mice"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-8186","authenticated-orcid":true,"given":"Sandip M.","family":"Swain","sequence":"first","affiliation":[{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle M-J","family":"Romac","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Vigna","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5498-4151","authenticated-orcid":true,"given":"Rodger A.","family":"Liddle","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University, Durham, North Carolina, USA."},{"name":"Department of Veterans Affairs Healthcare System, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)91022-A"},{"issue":"2","key":"B2","first-page":"149","article-title":"Pathomorphology of acute pancreatitis","volume":"66","author":"Kl\u00f6ppel","year":"1995","journal-title":"Ann Ital Chir"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.11.4.561"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506013322206"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(82)90008-3"},{"issue":"5","key":"B6","first-page":"408","article-title":"Chronic pancreatitis: evolution of the disease","volume":"38","author":"Kl\u00f6ppel","year":"1991","journal-title":"Hepatogastroenterology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-017-4602-2"},{"key":"B8","article-title":"Chronic pancreatitis","volume":"361","author":"Gupte","year":"2018","journal-title":"BMJ"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.033"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.03.054"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04194-9"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193270"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.015059"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.08.032"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87343"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.10.033"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65490-9"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.12.036"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65211-X"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30082"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.05.012"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.07369","article-title":"Chemical activation of the mechanotransduction channel Piezo1","volume":"4","author":"Syeda","year":"2015","journal-title":"Elife"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1021\/bi200770q"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI134111"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00502.2005"},{"key":"B26","unstructured":"Apte M. 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