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Expression profiling of apoptosis‐related genes in enterocytes isolated from patients with ulcerative colitis
Author(s) -
SEIDELIN JAKOB B.,
NIELSEN OLE H.
Publication year - 2006
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2006.apm_116.x
Subject(s) - ulcerative colitis , apoptosis , biology , cancer research , tumor necrosis factor alpha , gene expression profiling , inhibitor of apoptosis , population , immunology , colitis , gene expression , gene , microbiology and biotechnology , medicine , programmed cell death , pathology , genetics , disease , environmental health
Apoptosis regulation has been implicated as a main cause of epithelial dysfunction in patients with ulcerative colitis. Apoptosis can be divided into distinct pathways, which depend on the expression of a large number of apoptosis‐related genes. The aim was to elucidate which pathways are dominant in normal and inflamed colonic epithelial cells. An apoptosis‐specific gene array expression profiling system of 96 genes was used to determine the expression profile of apoptosis‐related genes. Epithelial cells isolated from three patients with active ulcerative colitis were pooled and compared to pooled epithelial cells isolated from three control subjects. Genes found to be three‐fold or more overexpressed in ulcerative colitis were subsequently analysed by PCR in a larger population (10 patients with ulcerative colitis, 8 control subjects). Selected genes found not to be regulated were additionally tested by PCR in the same population. Six genes were found to be highly expressed in epithelial cells from both controls and ulcerative colitis patients. These included Bcl‐2 antagonist/killer, B lymphoid tyrosine kinase, caspase 14, Harakiri, tumour necrosis factor (TNF) receptor 2, and TNF receptor‐associated factor 1 (TRAF1). Three genes were found to be upregulated in ulcerative colitis (p<0.01): caspase 1 and 5, and inhibitor of apoptosis protein 2 (c‐IAP2). Both receptor‐ and mitochondrion‐dependent apoptosis pathways are well expressed in enterocytes. Mainly activation‐dependent and cytoprotective genes were upregulated in ulcerative colitis.