{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:07:56Z","timestamp":1784117276741,"version":"3.55.0"},"reference-count":110,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute lung injury (ALI) attributable to sepsis or mechanical ventilation and subacute lung injury because of ionizing radiation (RILI) share profound increases in vascular permeability as a key element and a common pathway driving increased morbidity and mortality. Unfortunately, despite advances in the understanding of lung pathophysiology, specific therapies do not yet exist for the treatment of ALI or RILI, or for the alleviation of unremitting pulmonary leakage, which serves as a defining feature of the illness. A critical need exists for new mechanistic insights that can lead to novel strategies, biomarkers, and therapies to reduce lung injury. Sphingosine 1\u2013phosphate (S1P) is a naturally occurring bioactive sphingolipid that acts extracellularly via its G protein\u2013coupled S1P1\u20135 as well as intracellularly on various targets. S1P-mediated cellular responses are regulated by the synthesis of S1P, catalyzed by sphingosine kinases 1 and 2, and by the degradation of S1P mediated by lipid phosphate phosphatases, S1P phosphatases, and S1P lyase. We and others have demonstrated that S1P is a potent angiogenic factor that enhances lung endothelial cell integrity and an inhibitor of vascular permeability and alveolar flooding in preclinical animal models of ALI. In addition to S1P, S1P analogues such as 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol (FTY720), FTY720 phosphate, and FTY720 phosphonates offer therapeutic potential in murine models of lung injury. This translational review summarizes the roles of S1P, S1P analogues, S1P-metabolizing enzymes, and S1P receptors in the pathophysiology of lung injury, with particular emphasis on the development of potential novel biomarkers and S1P-based therapies for ALI and RILI.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0411tr","type":"journal-article","created":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T12:26:03Z","timestamp":1362140763000},"page":"6-17","source":"Crossref","is-referenced-by-count":129,"title":["Sphingosine-1\u2013Phosphate, FTY720, and Sphingosine-1\u2013Phosphate Receptors in the Pathobiology of Acute Lung Injury"],"prefix":"10.1093","volume":"49","author":[{"given":"Viswanathan","family":"Natarajan","sequence":"first","affiliation":[{"name":"Department of Pharmacology"},{"name":"Department of Medicine, and"},{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Dudek","sequence":"additional","affiliation":[{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Moreno-Vinasco","sequence":"additional","affiliation":[{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long Shuang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology"},{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taimur","family":"Abassi","sequence":"additional","affiliation":[{"name":"Department of Medicine, and"},{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biji","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Medicine, and"},{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, and"},{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bittman","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Queens College, City University of New York, Flushing, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Weichselbaum","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Berdyshev","sequence":"additional","affiliation":[{"name":"Department of Medicine, and"},{"name":"Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe G. 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