2026-06-14T03:36:00Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/55272024-10-31T11:39:14Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Strippoli, Raffaele author Loureiro, Jesus author Moreno, Vanessa author Benedicto, Ignacio author Perez Lozano, Maria Luisa author Barreiro, Olga author Pellinen, Teijo author Minguet, Susana author Foronda, Miguel author Osteso, Maria Teresa author Calvo, Enrique author Vazquez, Jesus author Lopez Cabrera, Manuel author del Pozo, Miguel Angel author 2015 Peritoneal dialysis (PD) is a form of renal replacement therapy whose repeated use can alter dialytic function through induction of epithelial-mesenchymal transition (EMT) and fibrosis, eventually leading to PD discontinuation. The peritoneum from Cav1(-/-) mice showed increased EMT, thickness, and fibrosis. Exposure of Cav1(-/-) mice to PD fluids further increased peritoneal membrane thickness, altered permeability, and increased the number of FSP-1/cytokeratin-positive cells invading the sub-mesothelial stroma. High-throughput quantitative proteomics revealed increased abundance of collagens, FN, and laminin, as well as proteins related to TGF-beta activity in matrices derived from Cav1(-/-) cells. Lack of Cav1 was associated with hyperactivation of a MEK-ERK1/2-Snail-1 pathway that regulated the Smad2-3/Smad1-5-8 balance. Pharmacological blockade of MEK rescued E-cadherin and ZO-1 inter-cellular junction localization, reduced fibrosis, and restored peritoneal function in Cav1(-/-) mice. Moreover, treatment of human PD-patient-derived MCs with drugs increasing Cav1 levels, as well as ectopic Cav1 expression, induced re-acquisition of epithelial features. This study demonstrates a pivotal role of Cav1 in the balance of epithelial versus mesenchymal state and suggests targets for the prevention of fibrosis during PD. EMBO Mol Med. 2015; 7(1):102-23 1757-4684 1757-4676 EMBO Molecular Medicine 25550395 http://hdl.handle.net/20.500.12105/5527 Caveolin-1 Epithelial-mesenchymal transition Fibrosis MEK-ERK1/2 pathway Peritoneal dialysis ENDOTHELIAL GROWTH-FACTOR E-CADHERIN EXPRESSION MAP KINASE PATHWAY NF-KAPPA-B MESOTHELIAL CELLS TGF-BETA TRANSCRIPTIONAL ACTIVITY QUANTITATIVE PROTEOMICS SCAFFOLDING DOMAIN PULMONARY DEFECTS Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial-mesenchymal transition and fibrosis during peritoneal dialysis