» Articles » PMID: 33076905

High Smad7 in the Early Post-operative Recurrence of Crohn's Disease

Overview
Journal J Transl Med
Publisher Biomed Central
Date 2020 Oct 20
PMID 33076905
Citations 6
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Colitis-associated carcinogenesis: crosstalk between tumors, immune cells and gut microbiota.

Li J, Ji Y, Chen N, Dai L, Deng H Cell Biosci. 2023; 13(1):194.

PMID: 37875976 PMC: 10594787. DOI: 10.1186/s13578-023-01139-8.


Smad7 as a positive regulator of intestinal inflammatory diseases.

Monteleone G, Laudisi F, Stolfi C Curr Res Immunol. 2023; 4:100055.

PMID: 36714553 PMC: 9881044. DOI: 10.1016/j.crimmu.2023.100055.


Regulatory T cells as a therapeutic approach for inflammatory bowel disease.

Laukova M, Glatman Zaretsky A Eur J Immunol. 2022; 53(2):e2250007.

PMID: 36562391 PMC: 10107179. DOI: 10.1002/eji.202250007.


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

Bai B, Li H, Han L, Mei Y, Hu C, Mei Q Mol Med Rep. 2022; 25(4).

PMID: 35137923 PMC: 8855156. DOI: 10.3892/mmr.2022.12632.


Current Trends in IBD-Development of Mucosal-Based Biomarkers and a Novel Minimally Invasive Recoverable Sampling System.

Yau Y, Wasinger V, Hirten R, Chuang E, Huntsman M, Stylli J Inflamm Bowel Dis. 2021; 27(Suppl 2):S17-S24.

PMID: 34791290 PMC: 9214562. DOI: 10.1093/ibd/izab179.


References
1.
Eftychi C, Schwarzer R, Vlantis K, Wachsmuth L, Basic M, Wagle P . Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment. Immunity. 2019; 51(2):367-380.e4. DOI: 10.1016/j.immuni.2019.06.008. View

2.
Strober W, Fuss I, Mannon P . The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007; 117(3):514-21. PMC: 1804356. DOI: 10.1172/JCI30587. View

3.
Fuss I, Neurath M, Boirivant M, Klein J, de La Motte C, Strong S . Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996; 157(3):1261-70. View

4.
Monteleone G, Pallone F, Macdonald T . Smad7 in TGF-beta-mediated negative regulation of gut inflammation. Trends Immunol. 2004; 25(10):513-7. DOI: 10.1016/j.it.2004.07.008. View

5.
Rutgeerts P, Geboes K, VANTRAPPEN G, KERREMANS R, Coenegrachts J, Coremans G . Natural history of recurrent Crohn's disease at the ileocolonic anastomosis after curative surgery. Gut. 1984; 25(6):665-72. PMC: 1432363. DOI: 10.1136/gut.25.6.665. View