title: Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver.
abstract: Cytoglobin (CYGB) is ubiquitously expressed in the cytoplasm of fibroblastic cells in many organs, including hepatic stellate cells. As yet, there is no specific marker with which to distinguish stellate cells from myofibroblasts in the human liver. To investigate whether CYGB can be utilized to distinguish hepatic stellate cells from myofibroblasts in normal and fibrotic human liver, human liver tissues damaged by infection with hepatitis C virus (HCV) and at different stages of fibrosis were obtained by liver biopsy. Immunohistochemistry was performed on histological sections of liver tissues using antibodies against CYGB, cellular retinol-binding protein-1 (CRBP-1), α-smooth muscle actin (α-SMA), thymocyte differentiation antigen 1 (Thy-1), and fibulin-2 (FBLN2). CYGB- and CRBP-1-positive cells were counted around fibrotic portal tracts in histological sections of the samples. The expression of several of the proteins listed above was examined in cultured mouse stellate cells. Quiescent stellate cells, but not portal myofibroblasts, expressed both CYGB and CRBP-1 in normal livers. In fibrotic and cirrhotic livers, stellate cells expressed both CYGB and α-SMA, whereas myofibroblasts around the portal vein expressed α-SMA, Thy-1, and FBLN2, but not CYGB. Development of the fibrotic stage was positively correlated with increases in Sirius red-stained, α-SMA-positive, and Thy-1-positive areas, whereas the number of CYGB- and CRBP-1-positive cells decreased with fibrosis development. Primary cultured mouse stellate cells expressed cytoplasmic CYGB at day 1, whereas they began to express α-SMA at the cellular margins at day 4. Thy-1 was undetectable throughout the culture period. In human liver tissues, quiescent stellate cells are CYGB positive. When activated, they also become α-SMA positive; however, they are negative for Thy-1 and FBLN2. Thus, CYGB is a useful marker with which to distinguish stellate cells from portal myofibroblasts in the damaged human liver.
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Motoyama
authors.affiliation: Department of Biological Function, Faculty of Science, Osaka City University, Osaka, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Komiya
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Le Thi Thanh
authors.initials: le TT
authors.lastname: Thuy
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Enomoto
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Morikawa
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Iwai
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Uchida-Kobayashi
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hagihara
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kawamura
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: 1] Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan [2] PhoenixBio, Higashihiroshima, Hiroshima, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
mesh_terms: D000199:Actins / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001391:Azo Compounds; D015415:Biomarkers / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000276:immunology; D002478:Cells, Cultured; D000078842:Cytoglobin; D016326:Extracellular Matrix Proteins / Q000276:immunology; D005914:Globins / Q000276:immunology* / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006526:Hepatitis C / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000378:metabolism*; D051379:Mice; D058628:Myofibroblasts / Q000378:metabolism; D018800:Thy-1 Antigens / Q000276:immunology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000906:Antibodies; D001391:Azo Compounds; D015415:Biomarkers; C000627265:CYGB protein, human; D002135:Calcium-Binding Proteins; C000627267:Cygb protein, mouse; D000078842:Cytoglobin; D016326:Extracellular Matrix Proteins; D018800:Thy-1 Antigens; C084612:fibulin 2; C062246:Direct Red 81; D005914:Globins