title: The reduction of allograft arteriosclerosis in intestinal transplant is associated with sphingosine kinase 1/sphingosine-1-phosphate signaling after fish oil treatment.
abstract: BACKGROUND
  Transplant arteriosclerosis is a major cause of late intestinal allograft dysfunction. However, little is known about the immunologic and molecular mechanisms underlying it, and no effective treatment is available. This study aimed to investigate the role of sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) in transplant arteriosclerosis and find out whether fish oil (FO) attenuates allograft arteriosclerosis through S1P signaling.
  
  
  METHODS
  A rat model with orthotopic intestinal transplantation was conducted in this study. Animals received daily FO supplementation after intestinal transplant. The allogeneic recipients by phosphate-buffered saline or corn oil treatment served as controls. The allograft arteriosclerosis was characterized, and the expression of SPHK1 and S1P receptors (S1P₁, S1P₂, and S1P₃) was determined on day 190 posttransplant.
  
  
  RESULTS
  The allogeneic controls presented transplant vasculopathy in mesenteric vessels, including intimal thickening, fibrosis, and leukocyte infiltration. The transplant arteriosclerosis was markedly reduced in FO-fed animals. The pression of SPHK1 and its activity were significantly augmented, and the expression of S1P₁ and S1P₃ messenger RNA was up-regulated in the allogeneic controls. FO supplementation suppressed the activation of SPHK1 and led to a decrease in the expression of S1P₁ and S1P₃ in these tissues in transplant arteriosclerosis.
  
  
  CONCLUSIONS
  These results demonstrate that the activation of SPHK1/S1P signaling plays a possible role in the pathogenesis of transplant arteriosclerosis. The reduction of allograft arteriosclerosis by FO may be associated with down-regulation of SPHK1/S1P signaling. Understanding the role of FO for SPHK1/S1P may help us to identify considerable therapeutic targets for transplant arteriosclerosis.
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Nanjing, People's Republic of China.
authors.forename: Qiurong
authors.initials: Q
authors.lastname: Li
authors.forename: Chenyang
authors.initials: C
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Tang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005395:Fish Oils / Q000494:pharmacology*; D007422:Intestines / Q000637:transplantation*; D008246:Lysophospholipids / Q000235:genetics / Q000502:physiology*; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology*; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D049349:Receptors, Lysosphingolipid / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000502:physiology; D014184:Transplantation, Homologous; D000099157:Sphingosine Kinase
chemical_list: D005395:Fish Oils; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate