{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:51:39Z","timestamp":1791305499411,"version":"4.3.1"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["P30-DK34989"],"award-info":[{"award-number":["P30-DK34989"]}]},{"name":"National Institutes of Health","award":["P01-DK57751"],"award-info":[{"award-number":["P01-DK57751"]}]},{"name":"National Institutes of Health","award":["R01-DK114041"],"award-info":[{"award-number":["R01-DK114041"]}]},{"name":"National Institutes of Health","award":["R01-DK112797"],"award-info":[{"award-number":["R01-DK112797"]}]},{"name":"National Institutes of Health","award":["R01-AA028765"],"award-info":[{"award-number":["R01-AA028765"]}]},{"name":"National Institutes of Health","award":["R01-AA031217"],"award-info":[{"award-number":["R01-AA031217"]}]},{"name":"National Institutes of Health","award":["S10-OD023598"],"award-info":[{"award-number":["S10-OD023598"]}]},{"name":"National Institutes of Health","award":["S10-OD020142"],"award-info":[{"award-number":["S10-OD020142"]}]},{"name":"National Institutes of Health","award":["R01-DK138584"],"award-info":[{"award-number":["R01-DK138584"]}]},{"name":"National Institutes of Health","award":["R01-DK121511"],"award-info":[{"award-number":["R01-DK121511"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Chronic liver disease affects over a billion people worldwide. Despite diverse etiologies, a unifying feature of chronic liver disease is the liver\u2019s impaired ability to regenerate during progression to cirrhosis, but no common molecular mechanism has been identified. Hepatocyte proliferation and liver regeneration depend on nucleoplasmic calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) signals, and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals in hepatocytes depend on the type 2 inositol trisphosphate receptor (ITPR2) calcium release channel. Here, we found that ITPR2 was localized in part to the hepatocyte nucleus, and this localization depended on the presence of nucleoporin 62 (NUP62). Loss of either ITPR2 or NUP62 disrupted nuclear Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling, and impaired Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals in the nucleus blunted nuclear entry of \u03b2-catenin. Remarkably, both ITPR2 and NUP62 are progressively lost from hepatocytes in patients with the four most common types of chronic liver disease. These findings identify a microdomain regulating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling in the hepatocyte nucleus that becomes progressively disrupted as liver disease progresses. Preservation of this nuclear microdomain may be a novel approach to maintain liver regeneration and slow the progression to cirrhosis in chronic liver disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.204059","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:46Z","timestamp":1791302446000},"source":"Crossref","is-referenced-by-count":0,"title":["Impaired regulation of nuclear calcium signals is a driver of chronic liver disease"],"prefix":"10.1172","author":[{"given":"Jittima","family":"Weerachayaphorn","sequence":"first","affiliation":[{"name":"Liver Center, Section of Digestive Diseases, Department of Internal Medicin, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus T.","family":"Guerra","sequence":"additional","affiliation":[{"name":"Liver Center, Section of Digestive Diseases, Department of Internal Medicin, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotaka","family":"Kugiyama","sequence":"additional","affiliation":[{"name":"Liver Center, Section of Digestive Diseases, Department of Internal Medicin, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Kruglov","sequence":"additional","affiliation":[{"name":"Liver Center, Section of Digestive Diseases, Department of Internal Medicin, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyachat","family":"Chansela","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Phramongkutklao College of Medicine, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitoon","family":"Saengsirisuwan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie E.","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruo","family":"Utsumi","sequence":"additional","affiliation":[{"name":"Liver Center, Section of Digestive Diseases, Department of Internal Medicin, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Iwakiri","sequence":"additional","affiliation":[{"name":"Liver Center, Section of Digestive Diseases, Department of Internal Medicin, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Nathanson","sequence":"additional","affiliation":[{"name":"Liver Center, Section of Digestive Diseases, Department of Internal Medicin, Yale University School of Medicine, New Haven, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,6]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/204059\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:46Z","timestamp":1791302446000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/204059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.204059"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.204059","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]}}}