Expression patterns of heat shock protein 25 in carbon tetrachloride-induced rat liver injury

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2013-07, Vol.65 (5), p.469-476
• Main Authors: Fujisawa, Kae, Yabuuchi, Chieko, Izawa, Takeshi, Kuwamura, Mitsuru, Takasu, Nobuo, Torii, Mikinori, Yamate, Jyoji
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; carbon; carbon tetrachloride; Carbon Tetrachloride - toxicity; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; chemokine CCL2; Data Interpretation, Statistical; Disease Models, Animal; gene expression; heat shock proteins; hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; Hsp25; HSP27 Heat-Shock Proteins - biosynthesis; HSP27 Heat-Shock Proteins - genetics; Immunohistochemistry; inflammation; liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Macrophage; macrophages; Male; messenger RNA; necrosis; oral administration; osteopontin; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger - biosynthesis; tumor necrosis factor-alpha
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2012.02.001

Heat shock protein 25 (Hsp25) is a molecular chaperone playing roles in cytoprotection. We investigated the distribution and localization of Hsp25 expression in CCl4-induced rat hepatic lesions; liver samples were obtained from 3h to 10days after a single oral administration of CCl4. Immunohistochemically, Hsp25-positive hepatocytes started to appear in the perivenular area at 6h after CCl4 administration. Their number and strength increased till day 1. Expression of Hsp25 mRNA significantly increased after 3h and proceeded to increase with time till day 1. Apoptotic hepatocytes were detected around the perivenular area after 6h. 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.