title: Hepatic stellate cells that coexpress LRAT and CRBP-1 partially contribute to portal fibrogenesis in patients with human viral hepatitis.
abstract: OBJECTIVE
  Precisely what type of cells mainly contributes to portal fibrosis, especially in chronic viral hepatitis, such as hepatic stellate cells (HSCs) in the parenchyma or myofibroblasts in the portal area, still remains unclear. It is necessary to clarify the characteristics of cells that contribute to portal fibrosis in order to determine the mechanism of portal fibrogenesis and to develop a therapeutic target for portal fibrosis. This study was undertaken to examine whether LRAT+/CRBP-1+ HSCs contribute to portal fibrosis on viral hepatitis.
  
  
  METHODS
  Antibodies to lecithin:retinol acyltransferase (LRAT), cellular retinol-binding protein-1 (CRBP-1) and widely ascertained antibodies to HSCs (alpha-smooth muscle actin, neurotrophin-3) and endothelial cells (CD31) were used for immunohistochemical studies to assess the distribution of cells that contribute to the development of portal fibrosis with the aid of fluorescence microscopy. A quantitative analysis of LRAT+/CRBP-1+ HSCs was performed.
  
  
  RESULTS
  The number of LRAT+/CRBP-1+ HSCs was increased in fibrotic liver in comparison with normal liver in the portal area and fibrous septa. The number of double positive cells was less than 20% of all cells/field in maximum.
  
  
  CONCLUSIONS
  This study provides evidence that functional HSCs coexpressing both LRAT and CRBP-1 that continue to maintain the ability to store vitamin A contribute in part to the development of portal fibrogenesis in addition to parenchymal fibrogenesis in patients with viral hepatitis.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan; Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagatsuma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murakami
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shindo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Jimi
authors.initials: J
authors.lastname: Mitobe
authors.forename: Ken
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masaya
authors.initials: M
authors.lastname: Saito
authors.forename: Haruka
authors.initials: H
authors.lastname: Maehashi
authors.forename: Mamiko
authors.initials: M
authors.lastname: Owada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikegami
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ohkusa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takagi
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsuura
mesh_terms: D000217:Acyltransferases / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006505:Hepatitis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011169:Portal Vein / Q000473:pathology*; D054840:Retinol-Binding Proteins, Cellular / Q000276:immunology / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism
chemical_list: D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase
keywords: Cellular retinol-binding protein-1 (CRBP-1); hepatic stellate (Ito) cell (HSC); lecithin retinol acyltransferase (LRAT); portal fibrosis; retinoid(vitamin A)