Elevated expression of tyrosine kinase DDR2 in primary biliary cirrhosis

Autoimmunity
Tin K MaoM E Gershwin

Abstract

Primary biliary cirrhosis (PBC) is characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and cholestasis, leading to fibrosis. We utilized a novel restriction analysis system to profile the expression of tyrosine kinases (TKs). This methodology targets a conserved sequence present in the majority of human TKs, and exploits the known restriction map of the TK cDNA sequences. We isolated mRNA from biliary epithelial cell (BEC)-enriched cell fractions, amplified the TK transcripts using degenerative primers, and identified specific TKs by restriction enzyme digest analysis and then performed in situ hybridization. BEC-enriched samples from PBC livers displayed marked expression of discoidin domain receptor-2 (DDR2), whereas, non-diseased livers showed no detectable DDR2. Furthermore, in situ hybridization of PBC livers revealed that DDR2 is expressed in the small bile duct epithelial regions as well as in fibroblasts/stromal cells of fibrotic regions. A similar pattern was observed in livers of primary sclerosing cholangitis (PSC), although the amount of small ducts that were positively stained was lower than in PBC. Furthermore, cirrhotic livers of patients with other diseases,...Continue Reading

Citations

Nov 16, 2010·Annual Review of Pathology·Virginia Hernandez-Gea, Scott L Friedman
Apr 22, 2006·Cellular Signalling·Wolfgang F VogelCaroline E Ford
Mar 2, 2011·The American Journal of Pathology·Sunmi SongMark D Gorrell
Oct 18, 2011·Biochemical and Biophysical Research Communications·Hye Youn SungJung-Hyuck Ahn
Jul 9, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Michitaka Matsuda, Ekihiro Seki

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