{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T10:45:29Z","timestamp":1778323529502,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["1ZIADE000695"],"award-info":[{"award-number":["1ZIADE000695"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Sj\u00f6gren's disease (SjD) has a strong sex bias, suggesting an association with sex hormones. Male SjD represents a distinct subset of the disease, but the pathogenic mechanisms of male SjD is poorly characterized. The aim of this study is to identify initiating events related to the development of gland hypofunction and autoimmunity in male SjD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Human minor salivary glands were transcriptomically analyzed with microarrays to detect differentially expressed genes in male SjD patients. Identified genes were tested on their involvement in the disease using conditional transgenic mice and gene\u2010overexpressing cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GPR78, an orphan G protein\u2013coupled receptor, was overexpressed in the salivary glands of male SjD patients compared with male healthy controls and female SjD patients. Male GPR78 transgenic mice developed salivary gland hypofunction with increased epithelial apoptosis, which was not seen in control or female transgenic mice. In cell culture, GPR78 overexpression decreased lysosomal integrity, leading to caspase\u2010dependent apoptotic cell death. GPR78\u2010induced cell death in vitro was inhibited by treatment with estradiol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GPR78 overexpression can induce apoptosis and salivary gland hypofunction in male mice through lysosomal dysfunction and increased caspase\u2010dependent apoptosis in salivary gland epithelium, which may drive disease in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.14506","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T13:42:48Z","timestamp":1674049368000},"page":"1173-1182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Association of G protein\u2010coupled receptor 78 with salivary dysfunction in male Sj\u00f6gren's patients"],"prefix":"10.1111","volume":"30","author":[{"given":"Tsutomu","family":"Tanaka","sequence":"first","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2633-9710","authenticated-orcid":false,"given":"Maria C.","family":"Guimaro","sequence":"additional","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2149-7573","authenticated-orcid":false,"given":"Hiroyuki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Perez","sequence":"additional","affiliation":[{"name":"Salivary Disorder Unit, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngmi","family":"Ji","sequence":"additional","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drew G.","family":"Michael","sequence":"additional","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra A.","family":"Afione","sequence":"additional","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changyu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, National Institute of Dental and Craniofacial Research National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William D.","family":"Swaim","sequence":"additional","affiliation":[{"name":"Adeno\u2010Associated Virus Biology Section, 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