Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal

J P Burke1, R W G Watson, J J Mulsow

  • 1Department of Surgery, St Vincent's University Hospital, Dublin, Ireland.

Abstract

Insights

Fibroblasts in Crohn's disease strictures show higher endoglin levels, which negatively regulate transforming growth factor-beta1 (TGF-β1) signaling. Reducing endoglin enhances TGF-β1 responses, impacting intestinal fibrosis.

Area of Science:

  • Gastroenterology
  • Cell Biology
  • Molecular Biology

Background:

  • Crohn's disease (CD) strictures involve fibroblast-mediated intestinal fibrosis.
  • Transforming growth factor-beta1 (TGF-β1) signaling is critical in this process.
  • Endoglin, a membrane glycoprotein, acts as a negative regulator of TGF-β1.

Purpose of the Study:

  • To investigate the role of endoglin in intestinal fibroblasts from CD strictures.
  • To determine if endoglin modulates TGF-β1 signaling in these cells.

Main Methods:

  • Cultured intestinal fibroblasts from CD stricture and control patients.
  • Assessed endoglin expression via microscopy, flow cytometry, and western blot.
  • Utilized siRNA and plasmid transfection to manipulate endoglin levels and measured TGF-β1 pathway activation (smad phosphorylation, SBE activity, CTGF, collagen contraction).

Main Results:

  • Fibroblasts from CD strictures exhibited increased constitutive endoglin expression.
  • Endoglin knockdown enhanced TGF-β1-induced smad-3 phosphorylation and collagen contraction.
  • Endoglin overexpression blocked TGF-β1-mediated SBE promoter activity and CTGF production.

Conclusions:

  • Increased endoglin in CD stricture fibroblasts negatively regulates TGF-β1 signaling.
  • Endoglin modulates key fibrotic pathways including smad phosphorylation, CTGF production, and collagen contraction.
  • Targeting endoglin may offer a therapeutic strategy for CD strictures.

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