Factor VII Transcription Correlates with Hepatocyte Proliferation and Hepatocyte Growth Factor Expression in a Rodent Extrahepatic Portal Vein Obstruction Model

Bill Chiu, Hector Melin-Aldana, Srikumar Pillai, Fei Chu, Riccardo A Superina*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Extrahepatic portal vein obstruction (EHPVO) is clinically associated with decreased liver-dependent coagulation factors and smaller than normal liver volumes. We developed a rodent EHPVO model to describe changes in coagulation factor regulation and liver homeostasis. Study Design: Fifteen rats underwent controlled narrowing of the portal vein (PV) at the hilum, and 15 underwent sham operations. Three animals from each group were sacrificed at postoperative days (PODs) 1, 2, 4, 7, and 21. Their livers were studied for apoptosis, proliferation, and hepatocyte growth factor (HGF) expression using terminal transferase dUTP nick end labeling (TUNEL) assays, Ki-67, and hepatocyte growth factor antibody. Liver total RNA was harvested for reverse transcriptase-polymerase chain reaction (RT-PCR), using primers for factors V, VII, VIII, X, protein C, and antithrombin. Appropriate statistical analysis was applied. Results: Ligation of the portal vein in the experimental group resulted in a 59 ± 17% (mean ± standard deviation) decrease in distal portal vein diameter. Proportional body weight was equivalent in both groups, but spleen weight was higher in the experimental group at PODs 4, 7, 21, and liver weight was higher at POD 7 (p < 0.05). The percentage of apoptotic cells in the experimental group increased from that of the control group at POD 4 (p < 0.05). The percentages of proliferating cells, HGF expression, and factor VII transcription in the experimental group were lower than those of controls at POD 2 (p < 0.05) but higher at POD 7 (p < 0.05). Ki-67/TUNEL double staining showed no grouping of apoptotic and proliferating cells. Factor V transcription in the experimental group was increased compared with that in controls at POD 2 (p < 0.05). Transcription of factors VIII, X, protein C, and antithrombin was unchanged. Conclusions: Our model demonstrated an early increase in hepatocyte apoptosis, impairment of factor VII transcription, and decrease in proliferative indices. These data support the hypothesis that EHPVO disrupts hepatic homeostasis and leads to dysregulation of coagulation factor synthesis.

Original languageEnglish (US)
Pages (from-to)277-283
Number of pages7
JournalJournal of the American College of Surgeons
Volume205
Issue number2
DOIs
StatePublished - Aug 1 2007

Fingerprint

Factor VII
Hepatocyte Growth Factor
Portal Vein
Hepatocytes
Rodentia
Liver
Blood Coagulation Factors
Factor V
Antithrombins
Transferases
Protein C
Homeostasis
Apoptosis
Weights and Measures
Factor VIII
Reverse Transcriptase Polymerase Chain Reaction
Ligation
Transcription Factors
Spleen
Body Weight

ASJC Scopus subject areas

  • Surgery

Cite this

@article{3983ec74a213440188b43ea777b6386c,
title = "Factor VII Transcription Correlates with Hepatocyte Proliferation and Hepatocyte Growth Factor Expression in a Rodent Extrahepatic Portal Vein Obstruction Model",
abstract = "Background: Extrahepatic portal vein obstruction (EHPVO) is clinically associated with decreased liver-dependent coagulation factors and smaller than normal liver volumes. We developed a rodent EHPVO model to describe changes in coagulation factor regulation and liver homeostasis. Study Design: Fifteen rats underwent controlled narrowing of the portal vein (PV) at the hilum, and 15 underwent sham operations. Three animals from each group were sacrificed at postoperative days (PODs) 1, 2, 4, 7, and 21. Their livers were studied for apoptosis, proliferation, and hepatocyte growth factor (HGF) expression using terminal transferase dUTP nick end labeling (TUNEL) assays, Ki-67, and hepatocyte growth factor antibody. Liver total RNA was harvested for reverse transcriptase-polymerase chain reaction (RT-PCR), using primers for factors V, VII, VIII, X, protein C, and antithrombin. Appropriate statistical analysis was applied. Results: Ligation of the portal vein in the experimental group resulted in a 59 ± 17{\%} (mean ± standard deviation) decrease in distal portal vein diameter. Proportional body weight was equivalent in both groups, but spleen weight was higher in the experimental group at PODs 4, 7, 21, and liver weight was higher at POD 7 (p < 0.05). The percentage of apoptotic cells in the experimental group increased from that of the control group at POD 4 (p < 0.05). The percentages of proliferating cells, HGF expression, and factor VII transcription in the experimental group were lower than those of controls at POD 2 (p < 0.05) but higher at POD 7 (p < 0.05). Ki-67/TUNEL double staining showed no grouping of apoptotic and proliferating cells. Factor V transcription in the experimental group was increased compared with that in controls at POD 2 (p < 0.05). Transcription of factors VIII, X, protein C, and antithrombin was unchanged. Conclusions: Our model demonstrated an early increase in hepatocyte apoptosis, impairment of factor VII transcription, and decrease in proliferative indices. These data support the hypothesis that EHPVO disrupts hepatic homeostasis and leads to dysregulation of coagulation factor synthesis.",
author = "Bill Chiu and Hector Melin-Aldana and Srikumar Pillai and Fei Chu and Superina, {Riccardo A}",
year = "2007",
month = "8",
day = "1",
doi = "10.1016/j.jamcollsurg.2007.04.005",
language = "English (US)",
volume = "205",
pages = "277--283",
journal = "Journal of the American College of Surgeons",
issn = "1072-7515",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Factor VII Transcription Correlates with Hepatocyte Proliferation and Hepatocyte Growth Factor Expression in a Rodent Extrahepatic Portal Vein Obstruction Model

AU - Chiu, Bill

AU - Melin-Aldana, Hector

AU - Pillai, Srikumar

AU - Chu, Fei

AU - Superina, Riccardo A

PY - 2007/8/1

Y1 - 2007/8/1

N2 - Background: Extrahepatic portal vein obstruction (EHPVO) is clinically associated with decreased liver-dependent coagulation factors and smaller than normal liver volumes. We developed a rodent EHPVO model to describe changes in coagulation factor regulation and liver homeostasis. Study Design: Fifteen rats underwent controlled narrowing of the portal vein (PV) at the hilum, and 15 underwent sham operations. Three animals from each group were sacrificed at postoperative days (PODs) 1, 2, 4, 7, and 21. Their livers were studied for apoptosis, proliferation, and hepatocyte growth factor (HGF) expression using terminal transferase dUTP nick end labeling (TUNEL) assays, Ki-67, and hepatocyte growth factor antibody. Liver total RNA was harvested for reverse transcriptase-polymerase chain reaction (RT-PCR), using primers for factors V, VII, VIII, X, protein C, and antithrombin. Appropriate statistical analysis was applied. Results: Ligation of the portal vein in the experimental group resulted in a 59 ± 17% (mean ± standard deviation) decrease in distal portal vein diameter. Proportional body weight was equivalent in both groups, but spleen weight was higher in the experimental group at PODs 4, 7, 21, and liver weight was higher at POD 7 (p < 0.05). The percentage of apoptotic cells in the experimental group increased from that of the control group at POD 4 (p < 0.05). The percentages of proliferating cells, HGF expression, and factor VII transcription in the experimental group were lower than those of controls at POD 2 (p < 0.05) but higher at POD 7 (p < 0.05). Ki-67/TUNEL double staining showed no grouping of apoptotic and proliferating cells. Factor V transcription in the experimental group was increased compared with that in controls at POD 2 (p < 0.05). Transcription of factors VIII, X, protein C, and antithrombin was unchanged. Conclusions: Our model demonstrated an early increase in hepatocyte apoptosis, impairment of factor VII transcription, and decrease in proliferative indices. These data support the hypothesis that EHPVO disrupts hepatic homeostasis and leads to dysregulation of coagulation factor synthesis.

AB - Background: Extrahepatic portal vein obstruction (EHPVO) is clinically associated with decreased liver-dependent coagulation factors and smaller than normal liver volumes. We developed a rodent EHPVO model to describe changes in coagulation factor regulation and liver homeostasis. Study Design: Fifteen rats underwent controlled narrowing of the portal vein (PV) at the hilum, and 15 underwent sham operations. Three animals from each group were sacrificed at postoperative days (PODs) 1, 2, 4, 7, and 21. Their livers were studied for apoptosis, proliferation, and hepatocyte growth factor (HGF) expression using terminal transferase dUTP nick end labeling (TUNEL) assays, Ki-67, and hepatocyte growth factor antibody. Liver total RNA was harvested for reverse transcriptase-polymerase chain reaction (RT-PCR), using primers for factors V, VII, VIII, X, protein C, and antithrombin. Appropriate statistical analysis was applied. Results: Ligation of the portal vein in the experimental group resulted in a 59 ± 17% (mean ± standard deviation) decrease in distal portal vein diameter. Proportional body weight was equivalent in both groups, but spleen weight was higher in the experimental group at PODs 4, 7, 21, and liver weight was higher at POD 7 (p < 0.05). The percentage of apoptotic cells in the experimental group increased from that of the control group at POD 4 (p < 0.05). The percentages of proliferating cells, HGF expression, and factor VII transcription in the experimental group were lower than those of controls at POD 2 (p < 0.05) but higher at POD 7 (p < 0.05). Ki-67/TUNEL double staining showed no grouping of apoptotic and proliferating cells. Factor V transcription in the experimental group was increased compared with that in controls at POD 2 (p < 0.05). Transcription of factors VIII, X, protein C, and antithrombin was unchanged. Conclusions: Our model demonstrated an early increase in hepatocyte apoptosis, impairment of factor VII transcription, and decrease in proliferative indices. These data support the hypothesis that EHPVO disrupts hepatic homeostasis and leads to dysregulation of coagulation factor synthesis.

UR - http://www.scopus.com/inward/record.url?scp=34447629864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447629864&partnerID=8YFLogxK

U2 - 10.1016/j.jamcollsurg.2007.04.005

DO - 10.1016/j.jamcollsurg.2007.04.005

M3 - Article

VL - 205

SP - 277

EP - 283

JO - Journal of the American College of Surgeons

JF - Journal of the American College of Surgeons

SN - 1072-7515

IS - 2

ER -