{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T07:16:33Z","timestamp":1777965393837,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:00:00Z","timestamp":1633824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-42546, MOP-119514, PJT-148847"],"award-info":[{"award-number":["MOP-42546, MOP-119514, PJT-148847"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Research and Innovation of Ontario","award":["RE-08-029"],"award-info":[{"award-number":["RE-08-029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation. Cell morphology, viability, and transcriptomic profiles were studied. Ischemia-reperfusion injury induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in the vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effect on these phenotypic characteristics. After CIT 18 h, protein-biosynthesis-related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene clusters in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell-type-dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.<\/jats:p>","DOI":"10.3390\/cells10102713","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:19:32Z","timestamp":1633900772000},"page":"2713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Ischemia-Reperfusion Injury in a Simulated Lung Transplant Setting Differentially Regulates Transcriptomic Profiles between Human Lung Endothelial and Epithelial Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Gaowa","family":"Saren","sequence":"first","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Wong","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"},{"name":"Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Bi","family":"Lu","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"},{"name":"Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Baciu","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Zamel","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahar","family":"Soltanieh","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichi","family":"Sugihara","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9188-8417","authenticated-orcid":false,"given":"Mingyao","family":"Liu","sequence":"additional","affiliation":[{"name":"Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada"},{"name":"Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1X8, Canada"},{"name":"Department of Surgery, Medicine and Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1902222","DOI":"10.1183\/13993003.02222-2019","article-title":"Potential Therapeutic Targets for Lung Repair during Human Ex Vivo Lung Perfusion","volume":"55","author":"Wong","year":"2020","journal-title":"Eur. 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