ZFIN ID: ZDB-PUB-130904-7
Role of hepsin in factor VII activation in zebrafish
Khandekar, G., and Jagadeeswaran, P.
Date: 2014
Source: Blood cells, molecules & diseases   52(1): 76-81 (Journal)
Registered Authors: Jagadeeswaran, Pudur, Khandekar, Gauri
Keywords: Factor VIIa, Factor VII, Hepsin, Factor VII activating protease, Vivo morpholino, Zebrafish
MeSH Terms:
  • Animals
  • Blood Coagulation/genetics*
  • Factor VII/antagonists & inhibitors
  • Factor VII/genetics*
  • Factor VII/metabolism
  • Factor VIIa/genetics*
  • Factor VIIa/metabolism
  • Factor Xa/administration & dosage
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Injections, Intravenous
  • Kinetics
  • Morpholinos/genetics
  • Morpholinos/metabolism
  • Oocytes/cytology
  • Oocytes/metabolism
  • Prothrombin Time
  • Serine Endopeptidases/genetics*
  • Serine Endopeptidases/metabolism
  • Signal Transduction
  • Xenopus laevis/genetics
  • Xenopus laevis/metabolism
  • Zebrafish/genetics*
  • Zebrafish/metabolism
PubMed: 23954211 Full text @ Blood Cells Mol. Dis.

Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish.