{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:15:46Z","timestamp":1793142946002,"version":"4.5.0"},"reference-count":59,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1R01HL140562"],"award-info":[{"award-number":["1R01HL140562"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2018,4,1]]},"abstract":"<jats:p>\n                    Zn\n                    <jats:sup>2+<\/jats:sup>\n                    is an essential element for cell survival\/growth, and its deficiency is linked to many disorders. Extracellular Zn\n                    <jats:sup>2+<\/jats:sup>\n                    concentration changes participate in modulating fundamental cellular processes such as proliferation, secretion, ion transport, and cell signal transduction in a mechanism that is not well understood. Here, we hypothesize that the Zn\n                    <jats:sup>2+<\/jats:sup>\n                    -sensing receptor ZnR\/G protein-coupled receptor 39 (GPR39), found in tissues where dynamic Zn\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis takes place, enables extracellular Zn\n                    <jats:sup>2+<\/jats:sup>\n                    to trigger intracellular signaling pathways regulating key cell functions in vascular cells. Thus, we investigated how extracellular Zn\n                    <jats:sup>2+<\/jats:sup>\n                    regulates cell viability, proliferation, motility, angiogenesis, vascular tone, and inflammation through ZnR\/GPR39 in endothelial cells. Knockdown of GPR39 through siRNA largely abolished Zn\n                    <jats:sup>2+<\/jats:sup>\n                    -triggered cellular activity changes, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    responses, as well as the downstream activation of G\u03b1q-PLC pathways. Extracellular Zn\n                    <jats:sup>2+<\/jats:sup>\n                    promoted vascular cell survival\/growth through activation of cAMP and Akt as well as overexpressing of platelet-derived growth factor-\u03b1 receptor and vascular endothelial growth factor A. It also enhanced cell adhesion and mobility, endothelial tubule formation, and cytoskeletal reorganization. Such effects from extracellular Zn\n                    <jats:sup>2+<\/jats:sup>\n                    were not observed in GPR39\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    endothelial cells. Zn\n                    <jats:sup>2+<\/jats:sup>\n                    also regulated inflammation-related key molecules such as heme oxygenase-1, selectin L, IL-10, and platelet endothelial cell adhesion molecule 1, as well as vascular tone-related prostaglandin I2 synthase and nitric oxide synthase-3. In sum, extracellular Zn\n                    <jats:sup>2+<\/jats:sup>\n                    regulates endothelial cell activity in a ZnR\/GPR39-dependent manner and through the downstream G\n                    <jats:sub>\u03b1<\/jats:sub>\n                    q-PLC pathways. Thus, ZnR\/GPR39 may be a therapeutic target for regulating endothelial activity.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00279.2017","type":"journal-article","created":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T17:17:03Z","timestamp":1513790223000},"page":"C404-C414","source":"Crossref","is-referenced-by-count":112,"title":["Zinc regulates vascular endothelial cell activity through zinc-sensing receptor ZnR\/GPR39"],"prefix":"10.1152","volume":"314","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3057-1889","authenticated-orcid":false,"given":"Donghui","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of North Texas, Denton, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchao","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of North Texas, Denton, 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