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Ectonucleotidase NTPDase2 is selectively down-regulated in biliary cirrhosis
Jonathan A Dranoff1, Emma A Kruglov, Joahd Toure
1Section of Digestive Diseases and Yale Liver Center, Yale University School of Medicine, One Gilbert Street, New Haven, CT 06520, USA. jonathan.dranoff@yale.edu
Summary
Loss of nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) in portal fibroblasts is a common feature of biliary cirrhosis in rats and humans. Its expression shifts in non-biliary cirrhosis, offering potential therapeutic targets.
Area of Science:
- Hepatology and liver disease research.
- Cell biology of liver fibrosis.
Background:
- Portal fibroblasts are distinct, fibrogenic liver cells.
- Nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) is normally found in portal fibroblasts.
- The behavior of NTPDase2 in cirrhosis was previously unknown.
Purpose of the Study:
- To investigate the impact of biliary cirrhosis on NTPDase2 expression in liver cells.
- To compare NTPDase2 changes in experimental rat models and human cirrhotic liver diseases.
Main Methods:
- Cirrhosis induced in rats using bile duct ligation (BDL) and carbon tetrachloride (CCl4).
- Analysis of human liver biopsies from normal, primary biliary cirrhosis, and hepatitis C cirrhosis.
- Assessed NTPDase2 expression via confocal immunofluorescence, immunoblot, and RT-PCR.
Main Results:
- BDL in rats decreased NTPDase2 expression in portal fibroblasts.
- CCl4 administration showed no decrease in NTPDase2 protein but increased mRNA, with expression shifting to alpha-smooth muscle actin-positive areas.
- Human biliary cirrhosis showed loss of NTPDase2; hepatitis C cirrhosis showed a shift to fibrous bands.
Conclusions:
- Loss of NTPDase2 is a shared characteristic of biliary cirrhosis in both rats and humans.
- Non-biliary cirrhosis involves a spatial shift of NTPDase2 expression.
- Understanding NTPDase2 regulation may reveal new therapeutic avenues for liver fibrosis.