title: Endothelial Sphingosine 1‑Phosphate Receptor‑1 Mediates Protection and Recovery from Acute Kidney Injury.
abstract: Epithelial and endothelial injury and a cascade of immune and interstitial cell activation in the kidney lead to AKI. After mild to moderate AKI, the epithelium can regenerate and restore kidney function, yet little is known about the endothelium during these repair processes. Sphingosine 1-phosphate receptor 1 (S1P1), a G protein-coupled receptor, is necessary for vascular homeostasis. Here, we used an inducible genetic approach in a mouse model of AKI, ischemia-reperfusion injury (IRI), to determine the temporal effects of endothelial S1P1 during AKI. Deletion of endothelial S1P1 before IRI exacerbated kidney injury and inflammation, and the delayed deletion of S1P1 after IRI prevented kidney recovery, resulting in chronic inflammation and progressive fibrosis. Specifically, S1P1 directly suppressed endothelial activation of leukocyte adhesion molecule expression and inflammation. Altogether, the data indicate activation of endothelial S1P1 is necessary to protect from IRI and permit recovery from AKI. Endothelial S1P1 may be a therapeutic target for the prevention of early injury as well as prevention of progressive kidney fibrosis after AKI.
authors.affiliation: Departments of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Perry
authors.affiliation: Departments of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine.
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.affiliation: Departments of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine.
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.affiliation: Microbiology, Immunology, and Cancer Biology, and.
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Departments of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine.
authors.forename: Sun-Sang J
authors.initials: SJ
authors.lastname: Sung
authors.affiliation: Pharmacology, University of Virginia, Charlottesville, Virginia.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Lynch
authors.affiliation: Pharmacology, University of Virginia, Charlottesville, Virginia.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Rosin
authors.affiliation: Departments of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine.
authors.forename: Amandeep
authors.initials: A
authors.lastname: Bajwa
authors.affiliation: Departments of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, mdo7y@virginia.edu ab9nh@virginia.edu.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D004727:Endothelium; D005355:Fibrosis / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049349:Receptors, Lysosphingolipid / Q000502:physiology* / Q000627:therapeutic use*; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000517:prevention & control
chemical_list: D049349:Receptors, Lysosphingolipid
keywords: acute renal failure; endothelium; fibrosis; inflammation