Endothelial sphingosine 1-phosphate receptor-1 mediates protection and recovery from acute kidney injury

Heather M. Perry, Liping Huang, Hong Ye, Chong Liu, Sun Sang J. Sung, Kevin R. Lynch, Diane L. Rosin, Amandeep Bajwa, Mark D. Okusa

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 andinflammation. Altogether, the data indicate activation of endothelial S1P1 is necessary to protect from IRI and permit recovery fromAKI. Endothelial S1P1may be a therapeutic target for the prevention of early injury as well as prevention of progressive kidney fibrosis after AKI.

Original languageEnglish (US)
Pages (from-to)3383-3393
Number of pages11
JournalJournal of the American Society of Nephrology
Volume27
Issue number11
DOIs
StatePublished - Jan 1 2016

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Lysosphingolipid Receptors
Acute Kidney Injury
Reperfusion Injury
Kidney
Wounds and Injuries
Fibrosis
Inflammation
Cell Adhesion Molecules
G-Protein-Coupled Receptors
Endothelium
Blood Vessels
Homeostasis
Epithelium

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Endothelial sphingosine 1-phosphate receptor-1 mediates protection and recovery from acute kidney injury. / Perry, Heather M.; Huang, Liping; Ye, Hong; Liu, Chong; Sung, Sun Sang J.; Lynch, Kevin R.; Rosin, Diane L.; Bajwa, Amandeep; Okusa, Mark D.

In: Journal of the American Society of Nephrology, Vol. 27, No. 11, 01.01.2016, p. 3383-3393.

Research output: Contribution to journalArticle

Perry, Heather M. ; Huang, Liping ; Ye, Hong ; Liu, Chong ; Sung, Sun Sang J. ; Lynch, Kevin R. ; Rosin, Diane L. ; Bajwa, Amandeep ; Okusa, Mark D. / Endothelial sphingosine 1-phosphate receptor-1 mediates protection and recovery from acute kidney injury. In: Journal of the American Society of Nephrology. 2016 ; Vol. 27, No. 11. pp. 3383-3393.
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