Blocking TGF-β1 protects the peritoneal membrane from dialysate-induced damage
Author
Loureiro, Joana A.; Aguilera, Abelardo I.; Selgas Gutiérrez, Rafael; Sandoval, Pilar; Albar-Vizcaíno, Patricia; Pérez-Lozano, María Luisa; Ruiz-Carpio, Vicente; Majano Rodríguez, Pedro Lorenzo; Lamas, Santiago; Rodríguez-Pascual, Fernando; Borrás-Cuesta, Francisco; Dotor, Javier; López-Cabrera, ManuelEntity
UAM. Departamento de MedicinaPublisher
American Society of NephrologyDate
2011-09-01Citation
10.1681/ASN.2010111197
Journal of the American Society of Nephrology 22.9 (2011): 1682-1695
ISSN
1046-6673 (print); 1553-3450 (online)DOI
10.1681/ASN.2010111197Funded by
This work was supported by grants SAF2010-21249 and SAF2007- 61201 from the Ministerio de Ciencia e Innovacio´n 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).Project
Gobierno de España. SAF2010-21249; Gobierno de España. SAF2007-61201Editor's Version
http://dx.doi.org/10.1681/ASN.2010111197Subjects
Peritoneal dialysis; TGF- β1; Cells; MedicinaRights
© 2011 by the American Society of NephrologyAbstract
During peritoneal dialysis (PD), mesothelial cells undergo mesothelial-to-mesenchymal transition (MMT), a
process associated with peritoneal-membrane dysfunction. Because TGF- 1 can induce MMT, we evaluated
the efficacy of TGF- 1-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 intermediatephenotype
(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- 1 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- 1 drives
the peritoneal deterioration induced by dialysis fluid and highlights a role of TGF- 1-mediated MMT in the
pathophysiology of peritoneal-membrane dysfunction
Files in this item
Google Scholar:Loureiro, Joana A.
-
Aguilera, Abelardo I.
-
Selgas Gutiérrez, Rafael
-
Sandoval, Pilar
-
Albar-Vizcaíno, Patricia
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Pérez-Lozano, María Luisa
-
Ruiz-Carpio, Vicente
-
Majano Rodríguez, Pedro Lorenzo
-
Lamas, Santiago
-
Rodríguez-Pascual, Fernando
-
Borrás-Cuesta, Francisco
-
Dotor, Javier
-
López-Cabrera, Manuel
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