{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:41:11Z","timestamp":1792788071709,"version":"4.5.0"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R01 GM111305-01 (KR)"],"award-info":[{"award-number":["R01 GM111305-01 (KR)"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R01 GM111305-01 (KR)"],"award-info":[{"award-number":["R01 GM111305-01 (KR)"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002613","name":"National  Institute of Science","doi-asserted-by":"crossref","award":["R01 GM111305-01 (KR)."],"award-info":[{"award-number":["R01 GM111305-01 (KR)."]}],"id":[{"id":"10.13039\/501100002613","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R01 GM111305-01 (KR)"],"award-info":[{"award-number":["R01 GM111305-01 (KR)"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,22]]},"abstract":"<jats:p>\n                    Lung contusion and gastric aspiration (LC and GA) are major risk factors for developing acute respiratory distress following trauma. Hypoxia from lung injury is mainly regulated by hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1). Published data from our group indicate that HIF-1\u03b1 regulation in airway epithelial cells (AEC) drives the acute inflammatory response following LC and GA. Metabolomic profiling and metabolic flux of Type II AEC following LC revealed marked increases in glycolytic and TCA intermediates in vivo and in vitro that were HIF-1\u03b1 dependent. GLUT-1\/4 expression was also increased in HIF-1\u03b1\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice, suggesting that increased glucose entry may contribute to increased intermediates. Importantly, lactate incubation in vitro on Type II cells did not significantly increase the inflammatory byproduct IL-1\u03b2. Contrastingly, succinate had a direct proinflammatory effect on human small AEC by IL-1\u03b2 generation in vitro. This effect was reversed by dimethylmalonate, suggesting an important role for succinate dehydrogenase in mediating HIF-1\u03b1 effects. We confirmed the presence of the only known receptor for succinate binding, SUCNR1, on Type II AEC. These results support the hypothesis that succinate drives HIF-1\u03b1\u2013mediated airway inflammation following LC. This is the first report to our knowledge of direct proinflammatory activation of succinate in nonimmune cells such as Type II AEC in direct lung injury models.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.166860","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T14:00:49Z","timestamp":1695304849000},"source":"Crossref","is-referenced-by-count":18,"title":["Role of succinate in airway epithelial cell regulation following traumatic lung injury"],"prefix":"10.1172","volume":"8","author":[{"given":"Madathilparambil V.","family":"Suresh","sequence":"first","affiliation":[{"name":"Department of Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinan","family":"Aktay","sequence":"additional","affiliation":[{"name":"Department of Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Yalamanchili","sequence":"additional","affiliation":[{"name":"Department of Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumeet","family":"Solanki","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dily Thazhath","family":"Sathyarajan","sequence":"additional","affiliation":[{"name":"Department of Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manikanta Swamy","family":"Arnipalli","sequence":"additional","affiliation":[{"name":"Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3628-6883","authenticated-orcid":true,"given":"Subramaniam","family":"Pennathur","sequence":"additional","affiliation":[{"name":"Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan","family":"Raghavendran","sequence":"additional","affiliation":[{"name":"Department of Surgery,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"B1"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421801"},{"issue":"10","key":"B3","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1177\/000313480206801002","article-title":"Acute respiratory distress syndrome in blunt trauma: identification of independent risk factors","volume":"68","author":"Miller","year":"2002","journal-title":"Am Surg"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0291"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001665"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1602079113"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805927200"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000000488"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001312"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90528.2008"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.022"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002070"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1096\/fba.2021-00132"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1199\/tab.0018"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01633"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.10.004"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13668-3"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/nu11010025"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3410\/B1-47"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00365"},{"issue":"2","key":"B21","article-title":"Oxidative pentose phosphate pathway enzyme 6-phosphogluconate dehydrogenase plays a key role in breast cancer metabolism","volume":"10","author":"Polat","year":"2021","journal-title":"Biology (Basel)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.064"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.11.022"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00390.2004"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-198608000-00002"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.030"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.621054"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700888R"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002778R"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2001-12-0169"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00052612"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.21.6.3751"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163694"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2012.00022"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000004644"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0358OC"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001879"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0175OC"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1021\/ac103313x"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0145"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.102960"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7428"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.12986"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/166860\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:48:50Z","timestamp":1779140930000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/166860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,22]]},"references-count":44,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9,22]]},"published-print":{"date-parts":[[2023,9,22]]}},"alternative-id":["10.1172\/jci.insight.166860"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.166860","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,22]]},"article-number":"e166860"}}