Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions
Abstract
Peritoneal adhesions (PAs) are fibrotic bands formed between bowel loops, solid organs, and the parietal peritoneum, which may appear following surgery, infection or endometriosis. They represent an important health problem with no effective treatment. Mesothelial cells (MCs) line the peritoneal cavity and undergo a mesothelial-to-mesenchymal transition (MMT) under pathological conditions, transforming into myofibroblasts, which are abundant in peritoneal fibrotic tissue. The aim of this study was to investigate if peritoneal MCs undergo a MMT contributing to the formation of post-surgical adhesions. Biopsies from patients with PAs were analysed by immunohistochemistry, immunofluorescence, and quantitative RT-PCR. A mouse model of PAs based on ischaemic buttons was used to modulate MMT by blocking the transforming growth factor-beta (TGF-β) pathway. The severity of adhesions and MMT-related marker expression were studied. We observed myofibroblasts derived from the conversion of MCs in submesothelial areas of patients with PAs. In addition, MMT-related markers were dysregulated in adhesion zones when compared to distant normal peritoneal tissue of the same patient. In animal experiments, blockage of TGF-β resulted in molecular reprogramming of markers related to the mesenchymal conversion of MCs and in a significant decrease in the severity of the adhesions. These data indicate for the first time that MMT is involved in PA pathogenesis. This finding opens new therapeutic strategies to interfere with adhesion formation by modulating MMT with a wide range of pharmacological agents.
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Mesothelial-to-mesenchymal transition in the peritoneal cavity is well known, with a specific role of platelets.
“Mesothelial-to-mesenchymal transition in the peritoneal cavity is well known (124, 125) with a specific role of platelets (48).”
From Pathogenesis of deep endometriosis (2017) · cites this paper as [124]
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- Authors
- Sandoval, P., Jiménez‐Heffernan, J. A., Guerra‐Azcona, G., Pérez‐Lozano, M. L., Rynne‐Vidal, Á., Albar‐Vizcaíno, P., Gil‐Vera, F., Martín, P., Coronado, M. J., Barcena, C., Dotor, J., Majano, P. L., Peralta, A. A., & López‐Cabrera, M.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Departamento de Anatomía Patológica Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IP) Madrid Spain
- Servicio de Cirugía Clínica Quirón‐San Camilo Madrid Spain
- Centro de Biología Molecular‐Severo Ochoa CSIC. Cantoblanco Madrid Spain
- Unidad de Biología Molecular y Servicio de Nefrología, Hospital Universitario La Princesa Instituto de Investigación Sanitaria Princesa (IP) Madrid Spain
- Hospital Universitario Puerta de Hierro Majadahonda (ES)
- Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria Hospital Puerta de Hierro Madrid Spain
- Departamento de Anatomía Patológica, Hospital Universitario 12 de Octubre Madrid Spain
- Digna Biotech Zizur Mayor Navarra Spain
- Hospital Universitario de La Princesa (ES)
- Corresponding author
- Peralta, Abelardo Aguilera
- ORCID
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2016-03-23
- Volume
- 239
- Issue
- 1
- Pages
- 48-59
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2302589752
- Cited by
- 116
- References
- 62
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 11 · 2023: 15 · 2022: 12 · 2021: 15 · 2020: 9 · 2019: 12 · 2018: 10 · 2017: 8 · 2016: 2
- FWCI
- 11.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministerio de Economia y Competitividad (SAF2013-47611R)
- Comunidad Autónoma de Madrid (S2010/BMD-2321)
- Fondo de Investigaciones Sanitarias (FIS)-FEDER funds (PI 15/00598)
- Instituto Carlos-III
- Topics
- Health Sciences › Medicine › Surgery › Intestinal and Peritoneal Adhesions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Keywords
- peritoneal adhesions, mesothelial-to-mesenchymal transition, mesothelial cells, myofibroblasts, TGF-beta signaling, postoperative adhesions, peritoneal fibrosis, adhesion prevention
- MeSH terms
- Actins, Tissue Adhesions, Adult, Aged, Animals, Female, Fibroblasts, Humans, Keratins, Male, Mice, Inbred C57BL, Middle Aged, Peptide Fragments, Peritoneum, Receptors, Transforming Growth Factor beta, Mice, Smad3 Protein, Young Adult, Epithelial-Mesenchymal Transition, Calbindin 2
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