2024-03-28T10:43:15Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/751522021-11-22T13:03:19Zcom_10261_79com_10261_1col_10261_332
Blocking TGF-β1 Protects the Peritoneal Membrane from Dialysate-Induced Damage
Loureiro, 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
Ministerio de Ciencia e Innovación (España)
Instituto de Salud Carlos III
Red Española de Investigación Renal
Digna Biotech
Fresenius Biotech
Baxter
Peritoneal dialysis
TGF-β1
Membrane dysfunction
During 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.
This work was supported by grants SAF2010-21249 and SAF2007-61201 from the Ministerio de Ciencia e Innovación to M.L.-C., by grants from Fondo de Investigaciones Sanitarias to R.S. (PI 09/0641) and A.A. (PI 07/00126), and from REDinREN (RETICS 06/0016, Fondos FEDER, EU) to R.S. This work was also partially supported by Digna Biotech, Fresenius Medical Care, and Baxter Healthcare Corporation (The Baxter Extramural Grant Program 2007).
Peer reviewed
2013-04-25T18:01:17Z
2013-04-25T18:01:17Z
2011
artículo
http://purl.org/coar/resource_type/c_6501
Journal of the American Society of Nephrology 22(9):1682-95 (2011)
1046-6673
http://hdl.handle.net/10261/75152
10.1681/ASN.2010111197
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100003389
http://dx.doi.org/10.13039/100007658
http://dx.doi.org/10.13039/501100004587
21742730
en
http://dx.doi.org/10.1681/ASN.2010111197
none
American Society of Nephrology