Abstract
Peritoneal adhesions, primarily caused by surgical procedures, are the leading cause of pelvic pain, bowel obstruction, and infertility. TGF-β1 and IL-6 have been found to be elevated in the peritoneal fluid of patients during/after abdominal surgery. However, it remains to be determined whether these cytokines interact and facilitate adhesion formation by promoting mesothelial to mesenchymal transition (MMT). In the present study, isolated rat peritoneal mesothelial cells were treated with TGF-β1 and/or IL-6 which elicited MMT as determined by morphologic and biochemical techniques. During this transition, cellular morphology changed from that of cobblestone polygonal cells to elongated/spindle-shaped fibroblast-like cells. There was decreased expression of genes characteristic of mesothelial cells, such as E-cadherin, and increased expression of genes characteristic of the myofibroblast phenotype, including α-smooth muscle actin and the EDA form of fibronectin, both of which appear to mediate the transfer of force to the extracellular matrix. Partial characterization of relevant signaling pathways identified Erk1/2 activation, which was enhanced by combined TGF-β1/IL-6 administration, as a crucial necessary factor in the tran...Continue Reading
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