Jill Roberts Center for Inflammatory Bowel Disease

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S1P₁ localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity.

TitleS1P₁ localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity.
Publication TypeJournal Article
Year of Publication2013
AuthorsMontrose DC, Scherl EJ, Bosworth BP, Zhou XKathy, Jung B, Dannenberg AJ, Hla T
JournalJ Lipid Res
Volume54
Issue3
Pagination843-51
Date Published2013 Mar
ISSN0022-2275
KeywordsAnimals, beta-Alanine, Capillary Permeability, Colitis, Ulcerative, Colon, Humans, Intestinal Mucosa, Male, Mice, Mice, Inbred C57BL, Propylene Glycols, Real-Time Polymerase Chain Reaction, Receptors, Lysosphingolipid, Sphingosine, Thiophenes
Abstract

Signaling through sphingosine-1-phosphate receptor₁ (S1P₁) promotes blood vessel barrier function. Degradation of S1P₁ results in increased vascular permeability in the lung and may explain side effects associated with administration of FTY720, a functional antagonist of the S1P₁ receptor that is currently used to treat multiple sclerosis. Ulcerative colitis (UC) is characterized by an increased density of abnormal vessels. The expression or role of S1P₁ in blood vessels in the colon has not been investigated. In the present study, we show that S1P₁ is overexpressed in the colonic mucosa of UC patients. This increase in S1P₁ levels reflects increased vascular density in the inflamed mucosa. Genetic deletion of S1pr1 in mice increases colonic vascular permeability under basal conditions and increases bleeding in experimental colitis. In contrast, neither FTY720 nor AUY954, two S1P receptor-targeting agents, increases bleeding in experimental colitis. Taken together, our findings demonstrate that S1P₁ is critical to maintaining colonic vascular integrity and may play a role in UC pathogenesis.

DOI10.1194/jlr.M034108
Alternate JournalJ. Lipid Res.
PubMed ID23296878
PubMed Central IDPMC3617958
Grant ListHL-67330 / HL / NHLBI NIH HHS / United States
HL-70694 / HL / NHLBI NIH HHS / United States
HL-89934 / HL / NHLBI NIH HHS / United States
T32 CA-062948 / CA / NCI NIH HHS / United States
T32 CA062948 / CA / NCI NIH HHS / United States