Diminished Piezo2-Dependent Tactile Sensitivity Occurs in Aging Human Gut and Slows Gastrointestinal Transit in Mice

See related article “Specialized mechanosensory epithelial cells in mouse gut intrinsic tactile sensitivity,” by Treichel AJ, Finholm I, Knutson KR, et al, Gastroenterology, 2022;162:535–547.e13. Enterochromaffin (EC) cell-derived serotonin is released in response to gut contraction 1 Keating D.J. et al. Gastroenterology. 2010; 138 (e1-e2): 659-670 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar to increase the frequency of these contractions and enhance gut motility. 1 Keating D.J. et al. Gastroenterology. 2010; 138 (e1-e2): 659-670 Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar ,2 Wei L. et al. Gastroenterology. 2021; 160: 2451-2466.e19 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Piezo2 is a nonselective cationic ion channel recently identified as an important mechanosensor in mouse EC cells. 3 Alcaino C. et al. Proc Natl Acad Sci U S A. 2018; 115: e7632-e7641 Crossref PubMed Scopus (117) Google Scholar There are no reports on human EC cell mechanosensing, the role of Piezo2 in this, and its relevance to in vivo gut motility. The data presented here demonstrate that Piezo2 is expressed in human EC cells where it regulates mechanically evoked serotonin release. We also identify an age-associated decrease in both mechanically evoked serotonin release and Piezo2 expression in EC cells. Our novel in vivo data in mice demonstrate the relevance of these findings as we show that the induced loss of Piezo2 expression specifically in EC cells drastically slows gut motility. See related article “Specialized mechanosensory epithelial cells in mouse gut intrinsic tactile sensitivity,” by Treichel AJ, Finholm I, Knutson KR, et al, Gastroenterology, 2022;162:535–547.e13. Specialized Mechanosensory Epithelial Cells in Mouse Gut Intrinsic Tactile SensitivityGastroenterologyVol. 162Issue 2PreviewA gut touch mechanism is described, which, like the skin’s touch, endows the intestine with tactile sense, which regulates motility in response to luminal forces and physical properties of contents. Full-Text PDF