title: Expression patterns of heat shock protein 25 in carbon tetrachloride-induced rat liver injury.
abstract: Heat shock protein 25 (Hsp25) is a molecular chaperone playing roles in cytoprotection. We investigated the distribution and localization of Hsp25 expression in CCl(4)-induced rat hepatic lesions; liver samples were obtained from 3 h to 10 days after a single oral administration of CCl(4). Immunohistochemically, Hsp25-positive hepatocytes started to appear in the perivenular area at 6 h after CCl(4) administration. Their number and strength increased till day 1. Expression of Hsp25 mRNA significantly increased after 3 h and proceeded to increase with time till day 1. Apoptotic hepatocytes were detected around the perivenular area after 6 h. The area where Hsp25-positive hepatocytes were observed till day 1 corresponded to the area where apoptotic hepatocytes were seen. On days 2 and 3, degenerative and/or necrotic hepatocytes in the perivenular area were replaced by macrophages reacting to ED1 (for CD68) and ED2 (for CD163); Hsp25 expression was seen in hepatocytes around the perivenular area and there was a close relationship of reactive macrophages with Hsp25-positive hepatocytes, suggesting a potential role for Hsp25 in suppressing injury by inflammation. The mRNA expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and osteopontin, which can be produced by infiltrating macrophages, corresponded to that of Hsp25 from day 1 to day 3; these factors might be related to the induction of Hsp25 expression. The shift of the Hsp25 expression pattern in the liver lesion might have depended on microenvironmental conditions evoked by interactions between necrobiotic hepatocytes and infiltrating macrophages. Thus, Hsp25 expression analyses should be beneficial for evaluations of hepatotoxicants.
authors.affiliation: Developmental Research Laboratories, Shionogi & co., Ltd, 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan. kae.fujisawa@shionogi.co.jp
authors.forename: Kae
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Chieko
authors.initials: C
authors.lastname: Yabuuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Takasu
authors.forename: Mikinori
authors.initials: M
authors.lastname: Torii
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; D012333:RNA, Messenger; D002251:Carbon Tetrachloride