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Ischemia reperfusion of the hepatic artery induces the functional damage of large bile ducts by changes in the expression of angiogenic factors
- Source :
- American Journal of Physiology-Gastrointestinal and Liver Physiology. 309:G865-G873
- Publication Year :
- 2015
- Publisher :
- American Physiological Society, 2015.
-
Abstract
- Liver transplantation and cholangiocarcinoma induce biliary dysfunction following ischemia reperfusion (IR). The function of the intrahepatic biliary tree is regulated by both autocrine and paracrine factors. The aim of the study was to demonstrate that IR-induced damage of cholangiocytes is associated with altered expression of biliary angiogenic factors. Normal and bile duct ligation rats underwent 24-h sham or hepatic reperfusion after 30 min of transient occlusion of the hepatic artery (HAIR) or portal vein (PVIR) before collecting liver blocks and cholangiocyte RNA or protein. We evaluated liver histology, biliary apoptosis, proliferation and expression of VEGF-A/C, VEGFR-2/3, Ang-1/2, and Tie-1/2 in liver sections and isolated small and large cholangiocytes. Normal rat intrahepatic cholangiocyte cultures (NRICC) were maintained under standard conditions in normoxic or under a hypoxic atmosphere for 4 h and then transferred to normal conditions for selected times. Subsequently, we measured changes in biliary proliferation and apoptosis and the expression of VEGF-A/C and VEGFR-2/3. In vivo, HAIR (but not PVIR) induced damage of large bile ducts and decreased proliferation and secretin-stimulated cAMP levels. HAIR-induced damage of large bile ducts was associated with increased expression of VEGF-A/C, VEGFR-2/3, Ang-1/2, and Tie-1/2. In vitro, under hypoxic conditions, there was increased apoptosis and reduced proliferation of NRICC concomitant with enhanced expression of VEGF-A/C and VEGFR-2/3. The functional damage of large bile ducts by HAIR and hypoxia is associated with increased expression of angiogenic factors in small cholangiocytes, presumably due to a compensatory mechanism in response to biliary damage.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
Pathology
Time Factors
Physiology
medicine.medical_treatment
Liver and Biliary Tract Physiology/Pathophysiology
Vascular Endothelial Growth Factor C
Apoptosis
Liver transplantation
Gastroenterology
Hepatic Artery
Cyclic AMP
Angiogenic Proteins
Cells, Cultured
Cholestasis
Cell Hypoxia
Up-Regulation
Reperfusion Injury
Liver Circulation
Signal Transduction
medicine.medical_specialty
angiogenic factors
Ischemia
Biology
liver
Cholangiocyte
Paracrine signalling
Secretin
Physiology (medical)
Internal medicine
medicine
Animals
biliary tree
RNA, Messenger
cholangiocytes
Cell Proliferation
transplantation
Hepatology
Vascular Endothelial Growth Factor Receptor-3
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
Rats, Inbred F344
Transplantation
Disease Models, Animal
Bile Ducts, Intrahepatic
Reperfusion injury
Subjects
Details
- ISSN :
- 15221547 and 01931857
- Volume :
- 309
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Accession number :
- edsair.doi.dedup.....779c9e79211250909a740d81c8cbd9d9
- Full Text :
- https://doi.org/10.1152/ajpgi.00015.2015