Epithelial-to-mesenchymal Transition of the Mesothelial Cell--its Role in the Response of the Peritoneum to Dialysis

Peritoneal membrane fibrosis, ranging from mild inflammation to severe sclerosing peritonitis, is one of the complications of peritoneal dialysis (PD). In parallel with fibrosis, the peritoneum shows a progressive increase of capillaries and vasculopathy, involved in increased small solute transport across the membrane and ultrafiltration failure. Glucose and glucose degradation products from PD solutions are responsible of stimulating transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) production by mesothelial cells (MCs). TGF-beta is a potent pro-fibrotic factor and inducer of epithelial-to-mesenchymal transition (EMT) of the MC. Local production of VEGF by transitional MC appears to play a central role in the processes leading to peritoneal angiogenesis. This review addresses the mechanism involved in peritoneal structural alteration by dialysis and points to the EMT of MC as the initiating mechanism of peritoneal injury. Information from multiple origins about TGF-beta and VEGF is integrated into EMT process in a comprehensive manner. Regulation and new targets for inhibition of EMT or its deleterious effects are discussed.