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Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions

Pilar Sandoval1, José A Jiménez-Heffernan2, Gonzalo Guerra-Azcona3

  • 1Centro de Biología Molecular-Severo Ochoa, CSIC. Cantoblanco, Madrid, Spain.

The Journal of Pathology
|April 14, 2016
PubMed

Insights

Peritoneal adhesions (PAs) form fibrotic bands after surgery. Mesothelial cells (MCs) transform into myofibroblasts, driving PA formation. Blocking TGF-β reduces adhesion severity, suggesting MMT modulation as a therapeutic strategy.

Area of Science:

  • Cell biology
  • Surgical pathology
  • Regenerative medicine

Background:

  • Peritoneal adhesions (PAs) are a significant post-surgical complication with no effective treatments.
  • Mesothelial cells (MCs) lining the peritoneum can transform into myofibroblasts, contributing to fibrotic tissue.
  • The role of mesothelial-to-mesenchymal transition (MMT) in PA pathogenesis remains unclear.

Purpose of the Study:

  • To investigate if peritoneal MCs undergo MMT in the formation of post-surgical adhesions.
  • To explore the potential of modulating MMT as a therapeutic strategy for PAs.

Main Methods:

  • Analysis of human PA biopsies using immunohistochemistry, immunofluorescence, and qRT-PCR.
  • Utilized a mouse model of PAs with ischemic buttons.
  • Modulated MMT by blocking the transforming growth factor-beta (TGF-β) pathway in the animal model.

Main Results:

  • Myofibroblasts derived from MC conversion were identified in human PA tissues.
  • MMT-related markers were dysregulated in adhesion zones compared to normal peritoneum.
  • Blocking TGF-β significantly reduced PA severity and altered MMT marker expression in mice.

Conclusions:

  • This study provides the first evidence that mesothelial-to-mesenchymal transition (MMT) plays a key role in the pathogenesis of peritoneal adhesions.
  • Targeting MMT offers a promising therapeutic avenue for preventing or treating post-surgical adhesions.
Keywords:
TGF-βmesothelial-to-mesenchymal transitionpost-surgical adhesions

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