English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/75152
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Blocking TGF-β1 Protects the Peritoneal Membrane from Dialysate-Induced Damage

AuthorsLoureiro, Jesús ; Aguilera, Abelardo; Selgas, Rafael; Sandoval, Pilar ; Albar-Vizcaíno, Patricia; Pérez-Lozano, María Luisa ; Ruiz-Carpio, Vicente ; Majano, Pedro L.; Lamas Peláez, Santiago ; Rodríguez-Pascual, Fernando ; Borras-Cuesta, Francisco; Dotor, Javier; López Cabrera, Manuel
KeywordsPeritoneal dialysis
Membrane dysfunction
Issue Date2011
PublisherAmerican Society of Nephrology
CitationJournal of the American Society of Nephrology 22(9):1682-95 (2011)
AbstractDuring peritoneal dialysis (PD), mesothelial cells undergo mesothelial-to-mesenchymal transition (MMT), a process associated with peritoneal-membrane dysfunction. Because TGF-β1 can induce MMT, we evaluated the efficacy of TGF-β1-blocking peptides in modulating MMT and ameliorating peritoneal damage in a mouse model of PD. Exposure of the peritoneum to PD fluid induced fibrosis, angiogenesis, functional impairment, and the accumulation of fibroblasts. In addition to expressing fibroblast-specific protein-1 (FSP-1), some fibroblasts co-expressed cytokeratin, indicating their mesothelial origin. These intermediate-phenotype (Cyto(+)/FSP-1(+)) fibroblasts had features of myofibroblasts with fibrogenic capacity. PD fluid treatment triggered the appearance of CD31(+)/FSP-1(+) and CD45(+)/FSP-1(+) cells, suggesting that fibroblasts also originate from endothelial cells and from cells recruited from bone marrow. Administration of blocking peptides significantly ameliorated fibrosis and angiogenesis, improved peritoneal function, and reduced the number of FSP-1(+) cells, especially in the Cyto(+)/FSP-1(+) subpopulation. Conversely, overexpression of TGF-β1 in the peritoneum by adenovirus-mediated gene transfer led to a marked accumulation of fibroblasts, most of which derived from the mesothelium. Taken together, these results demonstrate that TGF-β1 drives the peritoneal deterioration induced by dialysis fluid and highlights a role of TGF-β1-mediated MMT in the pathophysiology of peritoneal-membrane dysfunction.
Publisher version (URL)http://dx.doi.org/10.1681/ASN.2010111197
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.