Altered molecular pattern of mucosal healing in Crohn’s disease fibrotic stenosis

Abstract

To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry. TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-Neumann-Keuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e., basolateral area of the crypts and TNF-α very poorly expressed. Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by post-transcriptional regulation.