A novel function of thrombin-activatable fibrinolysis inhibitor during rat liver regeneration and in growth-promoted hepatocytes in primary culture.

Authors: Okumura, N  Koh, T  Hasebe, Y  Seki, T  Ariga, T 
Citation: Okumura N, etal., J Biol Chem. 2009 Jun 12;284(24):16553-61. doi: 10.1074/jbc.M109.011452. Epub 2009 Apr 22.
Pubmed: (View Article at PubMed) PMID:19386599
DOI: Full-text: DOI:10.1074/jbc.M109.011452

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.


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CRRD ID: 7243112
Created: 2013-05-03
Species: All species
Last Modified: 2013-05-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.