title: A novel function of thrombin-activatable fibrinolysis inhibitor during rat liver regeneration and in growth-promoted hepatocytes in primary culture.
abstract: Thrombin-activatable fibrinolysis inhibitor (TAFI) exhibits anti-fibrinolytic activity by removing C-terminal lysine residues from fibrin or plasminogen receptor proteins on the cellular surface, and plays an important role in the regulation of fibrinolysis. In this study, we examined the regulation of TAFI in hepatocytes during liver regeneration, and revealed its pivotal role in hepatocyte proliferation. In rat models, partial hepatectomy or carbon tetrachloride (CCl4)-induced acute liver injury suppressed the levels of plasma TAFI activity and hepatic TAFI mRNA, whereas this operation markedly increased both the hepatic plasmin activity and the level of proliferating cell nuclear antigen. In primary cultures of rat hepatocytes, the TAFI mRNA level was decreased under growth-promoting culture conditions. Treatment of the hepatocytes with TAFI siRNA increased the amount of plasmin on the hepatocytes and promoted hepatocyte proliferation. We concluded that TAFI regulates plasmin activity through its enzymatic activity whereby it reduces the plasminogen-binding capacity of the hepatocytes. The TAFI gene expression is down-regulated in hepatocyte proliferation for producing a fibrinolytic microenvironment suitable for cell growth. This is the first report on the role of TAFI in the pericellular fibrinolysis necessary for cellular proliferation.
authors.affiliation: From the Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, and the Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Kanagawa 252-8510, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Okumura
authors.affiliation: From the Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, and the Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Kanagawa 252-8510, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Koh
authors.affiliation: From the Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, and the Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Kanagawa 252-8510, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hasebe
authors.affiliation: From the Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, and the Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Kanagawa 252-8510, Japan. Electronic address: tseki@brs.nihon-u.ac.jp.
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Seki
authors.affiliation: From the Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, and the Department of Chemistry and Life Science, Nihon University College of Bioresource Sciences, Kanagawa 252-8510, Japan.
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Ariga
mesh_terms: D000208:Acute Disease; D000818:Animals; D002251:Carbon Tetrachloride; D025901:Carboxypeptidase B2 / Q000235:genetics* / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000502:physiology; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D008107:Liver Diseases / Q000503:physiopathology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002251:Carbon Tetrachloride; D025901:Carboxypeptidase B2