PERitoneal INflammation and Epithelial to Mesenchymal Transition (PERINEMT)

Title of TFM: Mesothelial-to-Mesenchymal Transition Induced by Mechanical Injury Is a Central Mechanism in the Development of Peritoneal Adhesions

     Peritoneal adhesions (PA) are fibrous tissues tethering organs to one another or to the peritoneal wall, leading to post-surgical morbidity and posing a major public health challenge. The primary chain of events leading to initiation of PA has been elusive, mainly due to a lack of traceable cells of origin. Mesothelial cells (MCs) line the peritoneum and undergo epithelial-to-mesenchymal transition (EMT) under pathological conditions, transforming into myofibroblasts. Intriguingly, we have recently demonstrated that mechanical stress triggers a robust EMT in MCs. In addition, we have shown that a cryptic matrix fragment of the laminin β1-chain, generated by MMP2 digestion, acts as modulators of the EMT process induced by TGFβ1. In this project the student will explore the molecular and biophysical determinants by which mechanical stretching acts as a potent EMT-inducing stimulus, and their modulation through the interaction of β1-fragment with α3β1 integrin. The results will add new insights in this emerging and specific contribution of mechanical cues to EMT in PA pathogenesis.