Differential expression in histologically normal crypts of ulcerative colitis suggests primary crypt disorder

Abstract

Ulcerative colitis is characterized by crypt infiltration particularly of neutrophils. However, it is not known whether it reflects a primary crypt disorder or a secondary inflammatory response. In this study, we analyzed the expression profiles of histologically normal crypts microdissected from formalin-fixed biopsies of early stage ulcerative colitis. Total RNAs were extracted, amplified, and applied to Affymetrix GeneChip(R) X3P Array. For the control, similar crypts from nonspecific colitis biopsies were applied. A total of 353 (4.3%) and 111 (1.4%) genes were >3 times up-, and down-regulated in ulcerative colitis. Up-regulated genes included FCGBP (Fc fragment of IgG binding protein), cyclophilin A, chemokine (C-X-C motif) ligand 3, and genes associated with lipid metabolism. Down-regulated genes included APOA4 (apolipoprotein A-IV), cylindromatosis, BCL2-like 10, claudin 8, and numerous transcriptional regulators. FCGBP and APOA4 have been implicated in ulcerative colitis previously. Our data show differential expression in the crypt epithelia of ulcerative colitis before active inflammation is initiated, suggesting primary crypt abnormalities that might be implicated in the pathogenesis of ulcerative colitis.