{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:45:56Z","timestamp":1792802756654,"version":"4.5.0"},"reference-count":53,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health Grants","doi-asserted-by":"crossref","award":["R01-DK134000"],"award-info":[{"award-number":["R01-DK134000"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health Grants","doi-asserted-by":"crossref","award":["R01-DK134028"],"award-info":[{"award-number":["R01-DK134028"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health Grants","doi-asserted-by":"crossref","award":["R01-DK138092"],"award-info":[{"award-number":["R01-DK138092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute kidney injury (AKI) is a leading cause of distant organ dysfunction among critically ill patients. Mitochondrial dysfunction is considered a key factor driving the damage after renal ischemia\u2013reperfusion (IR) injury. Damaged mitochondria release mitochondrial damage-associated molecular patterns (mtDAMPs) into the cytosol, which initiate a systemic inflammatory response. To better understand the underlying mechanism, mice were challenged with 30 min of bilateral renal ischemia followed by 24 h of reperfusion. The cytokine profiling in mouse lung tissues revealed that TREM-1 was significantly increased. Western Blot (WB) analysis demonstrated that the cGAS and STING pathway was increased in AKI mice. Transmission electron microscopy (TEM) images indicated that the mtDAMPs were released from damaged kidney mitochondria. Injection of mtDAMPs into mice induced an inflammatory response in the lungs similar to that induced by AKI. Mouse macrophages and lung epithelial cells were utilized to verify if inhibition of the TREM-1 and cGAS-STING pathways reduces mtDAMP-induced lung injury. Electric Cell-substrate Impedance Sensing (ECIS) results demonstrated that inhibiting the TREM-1 and cGAS-STING pathways significantly increased cell proliferation and migration while reducing mtDAMP-induced cytotoxicity. In conclusion, our findings suggest that targeting TREM-1 and cGAS-STING has the potential to attenuate acute lung injury in IR-AKI.<\/jats:p>","DOI":"10.3390\/cells14211716","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Acute Kidney Injury Induces Lung Damage via Mitochondrial DAMPs by Activating TREM-1 and cGAS-STING Pathways"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhi","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida (USF), 560 Channelside Dr., Tampa, FL 33602, USA"},{"name":"USF-TGH Transplant Research Center (UTRC), 560 Channelside Dr., Tampa, FL 33602, 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Y.","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida (USF), 560 Channelside Dr., Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nohely Hernandez","family":"Soto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida (USF), 560 Channelside Dr., Tampa, FL 33602, USA"},{"name":"USF-TGH Transplant Research Center (UTRC), 560 Channelside Dr., Tampa, FL 33602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose D.","family":"Herazo-Maya","sequence":"additional","affiliation":[{"name":"Ubben Center for Pulmonary Fibrosis Research, Morsani College of Medicine, University of South Florida (USF), 560 Channelside Dr., Tampa, FL 33602, 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