{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:29:46Z","timestamp":1792042186731,"version":"4.4.0"},"reference-count":83,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Approximately 10% of US births deliver preterm before 37\u00a0weeks of completed gestation. Premature infants are at risk for life\u2010long debilitating morbidities and death, and spontaneous preterm labour explains 50% of preterm births. In all cases existing treatments are ineffective, and none are FDA approved. The mechanisms that initiate preterm labour are not well understood but may result from dysfunctional regulation of quiescence mechanisms. Human pregnancy is accompanied by large increases in blood flow, and the uterus must enlarge by orders of magnitude to accommodate the growing fetus. This mechanical strain suggests that stretch\u2010activated channels may constitute a mechanism to explain gestational quiescence. Here we identify for the first time that Piezo1, a mechanosensitive cation channel, is present in the uterine smooth muscle and microvascular endothelium of pregnant myometrium. Piezo is downregulated during preterm labour, and stimulation of myometrial Piezo1 in an organ bath with the agonist Yoda1 relaxes the tissue in a dose\u2010dependent fashion. Further, stimulation of Piezo1 while inhibiting protein kinase A, AKT, or endothelial nitric oxide synthase mutes the negative inotropic effects of Piezo1 activation, intimating that actions on the myocyte and endothelial nitric oxide signalling contribute to Piezo1\u2010mediated contractile dynamics. Taken together, these data highlight the importance of stretch\u2010activated channels in pregnancy maintenance and parturition, and identify Piezo1 as a tocolytic target of interest.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15157-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Spontaneous preterm labour is a serious obstetric dilemma without a known cause or effective treatments.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Piezo1 is a stretch\u2010activated channel important to muscle contractile dynamics.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Piezo1 is present in the myometrium and is dysregulated in women who experience preterm labour.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Activation of Piezo1 by the agonist Yoda1 relaxes the myometrium in a dose\u2010dependent fashion, indicating that Piezo1\u00a0modulation may have therapeutic benefits to treat preterm labour.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp283299","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T04:23:52Z","timestamp":1660019032000},"page":"1675-1690","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Novel identification and modulation of the mechanosensitive Piezo1 channel in human myometrium"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2269-2525","authenticated-orcid":false,"given":"Scott D.","family":"Barnett","sequence":"first","affiliation":[{"name":"Department of Pharmacology Center for Molecular Medicine Reno School of Medicine University of Nevada Reno NV USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7556-575X","authenticated-orcid":false,"given":"Hazik","family":"Asif","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Center for Molecular Medicine Reno School of Medicine University of Nevada Reno NV USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-6137","authenticated-orcid":false,"given":"Iain L. 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