title: Analysis of glial fibrillary acidic protein (GFAP)-expressing ductular cells in a rat liver cirrhosis model induced by repeated injections of thioacetamide (TAA).
abstract: Glial fibrillary acidic protein (GFAP), a type III intermediate filament protein, is expressed in hepatic stellate cells (HSCs), the principal fibrogenic cell type in the liver. Further, GFAP could be a marker for hepatic progenitor cells (HPCs). In this study, the participation of GFAP-expressing cells in HPC expansion/ductular reaction was investigated in a rat model of liver cirrhosis. Six-week-old male F344 rats were injected intraperitoneally with thioacetamide (100mg/kg BW, twice a week) and examined at post-first injection weeks 5, 10, 15, 20 and 25. Fibrosis-related proliferation of ductular cells was observed as demonstrated by CK19 immunostaining. Some of these cells were stained with GFAP. No co-staining was observed between CK19 and α-smooth muscle actin (α-SMA; myofibroblast marker). There were proliferating ductular cells stained with α-fetoprotein or β-catenin; the ductular reaction was related to increased expression of hepatocarcinogenesis-related factors (Wnt2, Wnt4 and glypican-3). These results for the first time show the participation of GFAP-positive HPCs in ductular reaction in a chemically induced rodent model. Though the ductular cells were chaperoned by myofibroblasts, they show no direct evidence for epithelial to mesenchymal transition. These findings shed new light in understanding the roles of GFAP-expressing HPCs in liver cirrhosis and provide further evidence of interaction between newly-formed bile ductules and HSCs, suggesting that both cells could be in the common lineage of HPCs.
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Anusha H
authors.initials: AH
authors.lastname: Tennakoon
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Kavindra K
authors.initials: KK
authors.lastname: Wijesundera
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Katou-Ichikawa
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Miyuu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Hossain M
authors.initials: HM
authors.lastname: Golbar
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinku-ourai-kita, Izumisano City, Osaka, 598-8531, Japan. Electronic address: yamate@vet.osakafu-u.ac.jp.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D053673:Glypicans / Q000235:genetics / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D008297:Male; D058628:Myofibroblasts / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013853:Thioacetamide / Q000633:toxicity; D051154:Wnt2 Protein / Q000235:genetics / Q000378:metabolism; D060528:Wnt4 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D005326:Fetal Proteins; D005904:Glial Fibrillary Acidic Protein; D053673:Glypicans; D013853:Thioacetamide; D051154:Wnt2 Protein; D060528:Wnt4 Protein; D051176:beta Catenin; C498862:Acta2 protein, rat
keywords: Cirrhosis; Ductular reaction; Glial fibrillary acidic protein; Hepatic progenitor cells; Rat liver; Thioacetamide