title: Gene expression profiling of alcoholic liver disease in the baboon (Papio hamadryas) and human liver.
abstract: The molecular pathogenesis of alcoholic liver disease (ALD) is not well understood. Gene expression profiling has the potential to identify new pathways and altered molecules in ALD. Gene expression profiles of ALD in a baboon model and humans were compared using DNA arrays. Reverse transcriptase-polymerase chain reaction and immunohistochemistry were used for downstream analysis of array results. cDNA array analysis revealed differential expression of several novel genes and pathways in addition to genes known to be involved in ALD pathogenesis. Overall gene expression profiles were similar in both species, with a majority of genes involved with fibrogenesis and xenobiotic metabolism, as well as inflammation, oxidant stress, and cell signaling. Genes associated with stellate cell activation (collagens, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinase) were up-regulated in humans. Decreased expression of several metallothioneins was unexpected. Fourteen molecules related to the annexin family were up-regulated, including annexin A1 and A2. Immunofluorescence revealed a marked overexpression of annexin A2 in proliferating bile duct cells, hepatocyte cell surface, and selective co-localization with CD14-positive cells in human ALD. The gene expression profile of ALD is dominated by alcohol metabolism and inflammation and differs from other liver diseases. Annexins may play a role in the progression of fibrosis in ALD.
authors: Drug Health Services, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. phaber@mail.usyd.edu.au
authors: Devanshi
authors: D
authors: Seth
authors: Maria A
authors: MA
authors: Leo
authors: Peter H
authors: PH
authors: McGuinness
authors: Charles S
authors: CS
authors: Lieber
authors: Yvonne
authors: Y
authors: Brennan
authors: Rohan
authors: R
authors: Williams
authors: Xin M
authors: XM
authors: Wang
authors: Geoffrey W
authors: GW
authors: McCaughan
authors: Mark D
authors: MD
authors: Gorrell
authors: Paul S
authors: PS
authors: Haber
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010215:Papio