{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:16:18Z","timestamp":1788243378068,"version":"build-2803163510"},"reference-count":60,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100021002","name":"Fakultas Sains dan Teknik, Universitas Nusa Cendana","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The development of acute lung injury in COVID\u201019 patients is a major cause of lethality. Activation of the pulmonary vasculature, with inflammation, oxidative stress and barrier disruption, is initiated by the SARS\u2010CoV\u20102 spike protein (Sp1) at the endothelial cell surface. We previously identified the presence of a novel G\u2010Protein Coupled Receptor (GPCR) in the lung microvasculature, T1R3. The T1R3 agonist (T1R3\u2010A) protects the endothelium from endotoxin\u2010induced lung injury therefore we sought to investigate the effect of T1R3\u2010A on Sp1\u2010induced damage to the pulmonary endothelium. Sp1 induced significant disruption to the endothelium with elevated gap formation, monolayer leak and ROS accumulation. This damage was attenuated following exposure of the lung microvasculature to T1R3\u2010A. We further demonstrated that this agonist promotes ACE2 expression at the endothelial cell surface. Using immunoprecipitation studies, we demonstrated that T1R3\u2010A increases ACE2:T1R3 binding which may be a mechanism for protecting against Sp1\u2010induced endothelial cell injury. Our findings highlight the protective effect of T1R3 activation in the pulmonary endothelium and that there is a close link between T1R3 and ACE2. We propose that T1R3 activation protects the endothelium by preventing Sp1\u2010induced internalisation of ACE2, thereby blocking downstream ACE2 signalling leading to pulmonary vascular injury.<\/jats:p>","DOI":"10.1111\/jcmm.71339","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:54:37Z","timestamp":1787741677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>T1R3<\/scp>\n                    Anchors\n                    <scp>ACE2<\/scp>\n                    at the Pulmonary Endothelial Cell Surface to Attenuate Vascular Injury Following\n                    <scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20102 Spike 1 Protein Exposure In\u00a0Vitro"],"prefix":"10.1111","volume":"30","author":[{"given":"Zsuzsanna","family":"Kertesz","sequence":"first","affiliation":[{"name":"Centre for Biomedical Research and Health Innovation Anglia Ruskin University  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Spurrier\u2010Best","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research and Health Innovation Anglia Ruskin University  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-7583","authenticated-orcid":false,"given":"Havovi","family":"Chichger","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research and Health Innovation Anglia Ruskin University  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2021.05.003"},{"key":"e_1_2_10_3_1","unstructured":"M.Diamond H. 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