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, that 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 analyzed by immunohistochemistry, immunofluorescence and quantitative RT-PCR. A mouse model of PAs based on ischemic 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 modulated 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.

from #ORL-Sfakianakis via xlomafota13 on Inoreader http://ift.tt/1SwfS98
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from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1PsDA5c
via IFTTT