title: Extracellular matrix remodeling may predominate over hepatocyte injury in hepatocellular carcinoma development.
abstract: It has been suggested that both extracellular matrix (ECM) remodeling and persistent hepatocyte injury play important roles in liver carcinogenesis process. It is, however, still controversial which factor plays a predominant role. The aim of the present study was to examine the role of each factor in the liver enzyme-altered preneoplastic lesions, focusing on the relationship between the hepatocyte injury and fibrosis extension. The effects of two similar herbal medicines (Sho-saiko-to and Saiko-keishi-to: TJ-9 and TJ-10, respectively) were elucidated on the hepatocyte injury, fibrosis and preneoplastic lesions development using a choline-deficient-L-amino acid-defined (CDAA) diet rat liver carcinogenesis model. TJ-9 prevented fibrosis and glutathione S-transferase placental form (GST-P)-positive preneoplastic lesion development without reducing the hepatocyte injury as indicated by the serum markers. TJ-10 significantly protected against the hepatocyte injury. However, it did not exert any inhibitory effect on fibrosis and the development of preneoplastic lesions. Our in vitro study revealed that TJ-9 markedly suppressed the hepatic stellate cell activation whereas TJ-10 did not. These results suggested that the ECM remodeling plays a more important role than the persistent hepatocyte injury in the liver enzyme-altered preneoplastic lesion development in the rat.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kuriyama
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshii
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Noguchi
authors.forename: Koji
authors.initials: K
authors.lastname: Yanase
authors.forename: Tadashi
authors.initials: T
authors.lastname: Namisaki
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Tsujinoue
authors.forename: Hiroo
authors.initials: H
authors.lastname: Imazu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002796:Choline Deficiency / Q000150:complications; D004032:Diet; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000517:prevention & control; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D011230:Precancerous Conditions / Q000378:metabolism / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; C461320:shosaiko-to; C018142:saiko-keishi-to; D005982:Glutathione Transferase; D006909:Hydroxyproline