Genomic analysis of differentially expressed genes in liver and biliary epithelial cells of patients with primary biliary cirrhosis

Atsushi Tanaka, Patrick S Leung, Thomas P. Kenny, Janice Au-Young, Thomas P Prindiville, Ross L. Coppel, Aftab A. Ansari, M. Eric Gershwin

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The characterization of differentially expressed genes provides a powerful tool for identifying molecules that may be involved in the pathogenesis of disease. We have used two independent techniques to identify overexpressed transcripts in bile duct cells and in liver from patients with primary biliary cirrhosis (PBC). In the first method, we used suppressive subtractive hybridization to compare mRNA from isolated PBC bile duct epithelial cells (BECs) to normal BECs and identified 71 clones as transcribed at higher levels in PBC-BECs. Amongst these clones, 62/71 had matches in a non-redundant nucleotide database and 9/71 had matches in an EST database. Of the 62 clones, 51/62 include a complexity of genes involved in cell proliferation, signal transduction, transcription regulation, RNA processing, carbohydrate metabolism and hypothetical/unknown proteins; 4/62 were identified as interstitial collagenase and collagenase precursors, 4/62 as ribosomal proteins, 3/62 as mitochondrial DNA. The mitochondrial cDNA sequences included cytochrome c oxidase, Wnt-13, and the pHL gene, a c-myc oncogene containing coxIII sequence. In the second method, we constructed cDNA libraries from three different PBC livers and sequenced a total of 12,324 independent clones. These 12,324 clones underwent virtual subtraction with 2,814,148 independent clones from Incyte LifeSeq® libraries. Twenty one sequences were identified as unique to PBC liver. Collectively, these approaches identified a number of genes involved in signalling, RNA processing, mitochondrial function, inflammation, and fibrosis. Interestingly, both Wnt-13 and Notch transcripts are overexpressed in PBC liver. Further studies are needed to focus on the significance of these genes during the natural history of disease.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalJournal of Autoimmunity
Volume17
Issue number1
DOIs
StatePublished - Aug 1 2001

Fingerprint

Biliary Liver Cirrhosis
Clone Cells
Epithelial Cells
Bile Ducts
Liver
Genes
Databases
Matrix Metalloproteinase 1
myc Genes
Expressed Sequence Tags
Carbohydrate Metabolism
Collagenases
Electron Transport Complex IV
Mitochondrial DNA
Gene Library
Libraries
Signal Transduction
Fibrosis
Nucleotides
Complementary DNA

Keywords

  • Biliary epithelial cells
  • PBC
  • Subtractive hybridization

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Genomic analysis of differentially expressed genes in liver and biliary epithelial cells of patients with primary biliary cirrhosis. / Tanaka, Atsushi; Leung, Patrick S; Kenny, Thomas P.; Au-Young, Janice; Prindiville, Thomas P; Coppel, Ross L.; Ansari, Aftab A.; Gershwin, M. Eric.

In: Journal of Autoimmunity, Vol. 17, No. 1, 01.08.2001, p. 89-98.

Research output: Contribution to journalArticle

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