title: Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.
abstract: The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo Japan.
authors: Masaya
authors: M
authors: Sato
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo Japan.|CREST, JST, Japan.
authors: Hitoshi
authors: H
authors: Ikeda
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo Japan.
authors: Baasanjav
authors: B
authors: Uranbileg
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo Japan.|CREST, JST, Japan.
authors: Makoto
authors: M
authors: Kurano
authors: CREST, JST, Japan.|Department of Integrative Genomics, Tohoku Medical Megabank Organization, 2-1 Seiryo machi, Aobaku Sendai, Miyagi, Japan.
authors: Daisuke
authors: D
authors: Saigusa
authors: CREST, JST, Japan.|Graduate School of Pharmaceutical Science, Tohoku University, 6-3, Ara-makiazaaoba, Aobaku, Sendai, Miyagi, Japan.
authors: Junken
authors: J
authors: Aoki
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors: Harufumi
authors: H
authors: Maki
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors: Hiroki
authors: H
authors: Kudo
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors: Kiyoshi
authors: K
authors: Hasegawa
authors: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan.
authors: Norihiro
authors: N
authors: Kokudo
authors: Department of Clinical Laboratory Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo Japan.|CREST, JST, Japan.
authors: Yutaka
authors: Y
authors: Yatomi
mesh_terms: D000368:Aged; D027321:Anion Transport Proteins / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis*; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase
chemical_list: D027321:Anion Transport Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase; C477522:S1PR2 protein, human; C000598727:Spns2 protein, human