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Updated: Jun 13, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
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.
Background:
Fibroblasts isolated from strictures in Crohn's disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1.
Methods:
Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen.
Results:
Crohn's stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF.
Conclusion:
Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.
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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