tailieunhanh - Báo cáo khoa học: Hepatocyte growth factor activator (HGFA): its regulation by protein C inhibitor

Protein C inhibitor (PCI; SERPINA5) is a plasma serine protease inhibitor, and a potent inhibitor of activated protein C (APC), which plays a critical role in the anticoagulant protein C pathway. Recently, PCI was also found to form a complex with the serine protease hepatocyte growth factor activator (HGFA), inhibiting the HGFA-catalyzed activation of the single-chain hepatocyte growth factor precursor. | ỊFEBS Journal MINIREVIEW Hepatocyte growth factor activator HGFA its regulation by protein C inhibitor Koji Suzuki Department of Molecular Pathobiology Mie University Graduate Schoolof Medicine Japan Keywords activated protein C hepatocyte growth factor HGF HGF activator liver regeneration protein C inhibitor Correspondence K. Suzuki Department of Molecular Pathobiology Mie University Graduate Schoolof Medicine Edobashi 2-174 Tsu-city Mie 514-8507 Japan Fax 81 59 231 9797 Tel 81 59 231 9702 E-mail suzuki@ Received 30 November 2009 revised 29 January 2010 accepted 26 February 2010 doi Protein C inhibitor PCI SERPINA5 is a plasma serine protease inhibitor and a potent inhibitor of activated protein C APC which plays a critical role in the anticoagulant protein C pathway. Recently PCI was also found to form a complex with the serine protease hepatocyte growth factor activator HGFA inhibiting the HGFA-catalyzed activation of the singlechain hepatocyte growth factor precursor. In vivo studies using human PCI-transgenic hPCI-Tg mice which mimic PCI expression in humans showed that the regeneration rate of the liver after partial hepatectomy was significantly impaired as compared with wild-type mice. The decreased liver regeneration in hPCI-Tg mice was restored by pretreatment with antibody against human PCI. Furthermore APC protected hepatic nonparen-chymal cells from thrombin-induced inflammation in vitro suggesting that plasma PCI may inhibit the cytoprotective action of APC on hepatic cells in hPCI-Tg mice. It was shown that the levels of HGFA-PCI are increased in plasma of patients who have been subjected to hepatectomy as compared with complex levels in the plasma of normal individuals. Thus PCI may play a role as a potent inhibitor of HGFA and APC in plasma and or at the sites of tissue injury in the regulation of tissue regeneration. Introduction Protein C inhibitor PCI SERPINA5 a member of the plasma serine .