title: Epithelial to mesenchymal transition as a triggering factor of peritoneal membrane fibrosis and angiogenesis in peritoneal dialysis patients.
abstract: Peritoneal fibrosis (or sclerosis) is a complication of peritoneal dialysis (PD) and includes a wide spectrum of peritoneal structural changes, ranging from mild inflammation to severe sclerosing peritonitis and encapsulating-sclerosing peritonitis. In parallel with fibrosis, the peritoneum shows a progressive increase in capillary number (angiogenesis) and vasculopathy, which are involved in both the elevation of small solute transport across the peritoneal membrane and ultrafiltration failure. The most important substances from the PD solutions responsible for peritoneal deterioration are glucose and glucose degradation products, which stimulate transforming growth factor (TGF)beta and vascular endothelial growth factor (VEGF) production by mesothelial cells (MCs). TGFbeta is a potent pro-fibrotic factor and induces epithelial-mesenchymal transition (EMT) of the MC. Local production of VEGF during PD appears to play a central role in the processes leading to peritoneal neo-angiogenesis and functional decline. This review discusses the mechanisms implicated in peritoneal structural alteration and points to EMT of MC as the protagonist and initiator of peritoneal membrane injury, through an increment of the submesothelial fibroblast population. We also propose possible mechanisms of regulation and new targets for inhibition of EMT.
authors.affiliation: Servicios de Nefrología, Hospital Universitario de la Princesa, Diego de León 62, 28006 Madrid, Spain.
authors.forename: Abelardo
authors.initials: A
authors.lastname: Aguilera
authors.forename: Maria
authors.initials: M
authors.lastname: Yáñez-Mo
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Cabrera
mesh_terms: D004848:Epithelium / Q000473:pathology*; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis / Q000473:pathology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D010530:Peritoneal Dialysis; D010532:Peritoneal Diseases / Q000150:complications / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D010537:Peritoneum / Q000098:blood supply / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D005947:Glucose