High Smad7 in the early post-operative recurrence of Crohn’s disease

Abstract

Background In Crohn’s disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD. Methods Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry. Results Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-γ-secreting cells. Conclusions Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.

Regulatory T cells as a therapeutic approach for inflammatory bowel disease

“…Alternatively, it has been suggested that effector T cells in inflamed colons of patients with CD are uniquely able to evade Treg cell suppression through increased expression of Smad7, an inhibitor of TGF‐β1 signaling, which is a key mechanism of Treg suppressive function [61]. It has been proposed that the upregulation of Smad7 in the ileum of patients with CD is an early event in the inflammatory processes leading to CD [62].…”

Molecular mechanism of the TGF‑β/Smad7 signaling pathway in ulcerative colitis

“…A recent study has indicated that rigorous experimental design assist in furthering the understanding in the significance of Smad7 as a therapeutic target for IBD (36). in addition, Wu-Mei-Wan is a classic chinese medicine for treating digestive diseases and pervious study has shown that the antifibrotic effects of it may result from the inhibition of the TGF-β/Smad pathway (44), whilst knocking down Smad7 expression was found to be beneficial in preventing the post-operative recurrence of cd (45). Therefore, understanding the molecular characteristics of iBd will assist in the identification of novel candidates for the inhibition of Smad7.…”