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Updated: Sep 21, 2025

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
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IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn's Disease

Dulce C Macias-Ceja1, Sandra Coll1, Cristina Bauset1

  • 1CIBERehd (Centro de Investigaciones en Red Enfermedad Hepática y Digestiva), Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain.

Biomedicines
|May 28, 2022
PubMed
Abstract

Insights

In Crohn's disease (CD) fibrosis, a microenvironment rich in interferon-gamma (IFNγ) polarizes macrophages. These activated macrophages then induce epithelial-mesenchymal transition (EMT) via the WNT pathway.

Area of Science:

  • Gastroenterology
  • Immunology
  • Cell Biology

Background:

  • Fibrosis is a frequent complication of Crohn's disease (CD), with macrophages playing a key role.
  • Epithelial-mesenchymal transition (EMT) and the WNT pathway are implicated in fibrosis development.

Purpose of the Study:

  • To investigate the influence of the tissue microenvironment on macrophage phenotype.
  • To analyze the role of the microenvironment in the epithelial-mesenchymal transition (EMT) process.

Main Methods:

  • Intestinal tissues from control and CD patients were analyzed.
  • Macrophage phenotype, EMT markers, and WNT signaling were assessed using techniques like Western blot, RT-PCR, ELISA, and cytometry.
  • In vitro studies involved treating U937 cells with cytokines and co-culturing them with HT29 cells, with or without WNT pathway inhibitors.

Main Results:

  • Increased levels of interferon-gamma (IFNγ), WNT6, CD16, and CD86 were observed in CD patient tissues.
  • IFNγ stimulation induced EMT and activated the WNT pathway in HT29 cells.
  • The EMT process was found to be mediated by FZD4.

Conclusions:

  • An IFNγ-rich microenvironment polarizes macrophages.
  • Polarized macrophages induce EMT through the WNT pathway, contributing to fibrosis in Crohn's disease.
Keywords:
Crohn diseaseEpithelial Mesenchymal Transition (EMT)IFNγfibrosismacrophages

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