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Although we recently described the structure of the nuclear mechanotransducer that controls renin transcription, the acute pressure-sensing mechanism that controls the rapid release of renin has not been identified. In JG cells there is an inverse relationship between intracellular calcium and renin release, the \u2018calcium paradox\u2019. Since the discovery of Piezo2 as the \u2018touch\u2019 receptors, there has been a significant interest in exploring whether they are also involved in other tissues beyond the skin. Given that Piezo receptors are permeable to calcium upon mechanical stimuli, it would be reasonable to hypothesize that Piezo2 controls renin synthesis and\/or release in JG cells. To test this hypothesis, we used a variety of novel mouse models and JG cell-specific techniques to define whether Piezo2 controls renin expression and\/or release in JG cells. Our in vivo data using constitutive and inducible Cre driver mouse lines and a variety of novel experimental approaches indicate that Piezo2 channels are not necessary for renin synthesis or release in JG cells during normal conditions or when homeostasis is threatened by hypotension, sodium depletion, or inverse changes in blood pressure. Furthermore, Piezo1 channels do not compensate for the lack of Piezo2 in JG cells. Efforts should be devoted to identifying the acute mechanosensory mechanisms controlling renin release.<\/jats:p>","DOI":"10.1042\/cs20242089","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T10:07:05Z","timestamp":1732097225000},"page":"1527-1536","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Piezo channels in JG cells do not regulate renin expression or renin release to the circulation"],"prefix":"10.1042","volume":"138","author":[{"given":"Vidya\u00a0K.","family":"Nagalakshmi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason\u00a0P.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5124-8255","authenticated-orcid":false,"given":"Roberto\u00a0Ariel","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4459-7940","authenticated-orcid":false,"given":"Maria\u00a0Luisa\u00a0Soledad","family":"Sequeira-Lopez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"2024112912560616100_B1","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1161\/HYPERTENSIONAHA.123.20577","article-title":"Renin cells, from vascular development to blood pressure sensing","volume":"80","author":"Yamaguchi","year":"2023","journal-title":"Hypertension"},{"key":"2024112912560616100_B2","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1161\/CIRCRESAHA.120.318711","article-title":"Renin cell baroreceptor, a nuclear mechanotransducer central for homeostasis","volume":"129","author":"Watanabe","year":"2021","journal-title":"Circ. 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