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Constitutive and Inducible Systems for Genetic In Vivo Modification of Mouse Hepatocytes Using Hydrodynamic Tail Vein Injection
Published on: February 2, 2018
Hepatocyte tissue factor activates the coagulation cascade in mice.
Bradley P Sullivan1, Anna K Kopec, Nikita Joshi
1Department of Pathobiology and Diagnostic Investigation, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Blood
|January 12, 2013
Summary
Mouse hepatocytes (HPCs) express tissue factor (TF) on their surface, which activates blood coagulation. This TF plays a crucial role in liver injury and transplantation models.
Area of Science:
- Hepatology
- Hemostasis
- Biochemistry
Background:
- Tissue Factor (TF) is a key initiator of the coagulation cascade.
- Hepatocytes (HPCs) are crucial liver cells, but their role in hemostasis is not fully understood.
- Understanding TF expression in HPCs is vital for liver injury and transplantation research.
Purpose of the Study:
- To characterize TF expression in mouse HPCs.
- To investigate the role of HPC-derived TF in acetaminophen (APAP)-induced liver injury.
- To evaluate the significance of HPC TF in liver transplantation.
Main Methods:
- Generated and utilized TF-deficient hepatocyte-specific knockout mice (HPC(ΔTF) mice).
- Assessed TF expression and activity in isolated HPCs and liver tissues.
- Employed mouse models of APAP overdose and HPC transplantation.
- Measured thrombin generation in vivo and in vitro.
Main Results:
- HPC(ΔTF) mice exhibited significantly reduced TF expression compared to controls.
- Isolated HPCs expressed cell-surface TF that initiated Factor Xa generation, especially after lysis.
- Thrombin generation was markedly reduced in APAP-treated HPC(ΔTF) mice and dependent on donor HPC TF in transplantation models.
Conclusions:
- Mouse hepatocytes constitutively express functional cell-surface TF.
- HPC-derived TF is critical for activating coagulation during hepatocellular injury.
- TF expression in HPCs is a significant factor in liver injury pathogenesis and HPC transplantation efficacy.
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