{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:59:53Z","timestamp":1781812793960,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["23136505"],"award-info":[{"award-number":["23136505"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["25136708"],"award-info":[{"award-number":["25136708"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22K06659"],"award-info":[{"award-number":["22K06659"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22K06659DK"],"award-info":[{"award-number":["22K06659DK"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JKA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Transient receptor potential melastatin 2 (TRPM2) channel is a Ca2+-permeable, redox-activated cardiac ion channel protective in ischemia\u2013reperfusion, but whether it regulates atrial endocrine output under stress is unclear. Here, we investigated whether TRPM2 contributes to the atrial natriuretic peptide (ANP) response during \u03b2-adrenergic stimulation. We compared how male C57BL\/6J wild-type (WT) and TRPM2 knockout (TRPM2\u2212\/\u2212) mice (8\u201312 weeks old) respond to \u03b2-adrenergic stress induced by isoproterenol (ISO) using echocardiography, histology, RT-PCR, electrophysiology, Ca2+ imaging, ELISA, and atrial RNA-seq. We detected abundant Trpm2 transcripts in WT atria and measured ADP-ribose (ADPr)-evoked currents and hydrogen peroxide (H2O2)-induced Ca2+ influx characteristic of TRPM2; these were absent in TRPM2\u2212\/\u2212 cells. Under the ISO-induced hypertrophic model, TRPM2\u2212\/\u2212 mice developed greater cardiac hypertrophy, fibrosis, and systolic dysfunction compared with WT mice. Atrial bulk RNA-seq showed significant induction of Nppa (ANP precursor gene) in WT + ISO, accompanied by higher circulating ANP; TRPM2\u2212\/\u2212 + ISO showed blunted Nppa and ANP responses. ISO-treated TRPM2\u2212\/\u2212 mice exhibited more blunt responses, in both Nppa transcripts and circulating ANP levels. Exogenous ANP attenuated ISO-induced dysfunction, hypertrophy, and fibrosis in TRPM2\u2212\/\u2212 mice, suggesting that TRPM2 is needed for the cardioprotective endocrine response via ANP to control stress-induced \u03b2-adrenergic remodeling.<\/jats:p>","DOI":"10.3390\/cells15010024","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T16:19:26Z","timestamp":1766420366000},"page":"24","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Atrial TRPM2 Channel-Mediated Ca2+ Influx Regulates ANP Secretion and Protects Against Isoproterenol-Induced Cardiac Hypertrophy and Fibrosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5719-4884","authenticated-orcid":false,"given":"Tomohiro","family":"Numata","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Tagashira","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9369-4261","authenticated-orcid":false,"given":"Kaori","family":"Sato-Numata","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith C","family":"Hermosura","sequence":"additional","affiliation":[{"name":"John A. Burns School of Medicine, Honolulu, HI 96813, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3827-088X","authenticated-orcid":false,"given":"Fumiha","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo 164-8530, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Akita University Graduate School of Medicine, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"de Lucia, C., Eguchi, A., and Koch, W.J. 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