2024-03-28T11:05:26Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/324232018-09-12T11:48:24Zcom_10261_133com_10261_1com_10261_112col_10261_386col_10261_365
2011-02-16T11:29:36Z
urn:hdl:10261/32423
Deletion of H-Ras decreases renal fibrosis and myofibroblast activation following ureteral obstruction in mice
Grande, M. Teresa
Fuentes-Calvo, Isabel
Arévalo, Miguel
Heredia, Fabiana
Santos de Dios, Eugenio
Martínez-Salgado, Carlos
Rodríguez-Puyol, Diego
Nieto, M. Ángela
López-Novoa, José M.
Cell biology and structure
Extracellular matrix
Fibroblast
Interstitial fibrosis
Obstructive nephropathy
10 páginas.
Tubulointerstitial fibrosis is characterized by the presence of myofibroblasts that contribute to extracellular matrix accumulation. These cells may originate from resident fibroblasts, bone-marrow-derived cells, or renal epithelial cells converting to a mesenchymal phenotype. Ras GTPases are activated during renal fibrosis and play crucial roles in regulating both cell proliferation and TGF-β-induced epithelial–mesenchymal transition. Here we set out to assess the contribution of Ras to experimental renal fibrosis using the well-established model of unilateral ureteral obstruction. Fifteen days after obstruction, both fibroblast proliferation and inducers of epithelial–mesenchymal transition were lower in obstructed kidneys of H-ras knockout mice and in fibroblast cell lines derived from these mice. Interestingly, fibronectin, collagen I accumulation, overall interstitial fibrosis, and the myofibroblast population were also lower in the knockout than in the wild-type mice. As expected, we found lower levels of activated Akt in the kidneys and cultured fibroblasts of the knockout. Whether Ras inhibition will turn out to prevent progression of renal fibrosis will require more direct studies.
2011-02-16T11:29:36Z
2011-02-16T11:29:36Z
2010-03-02
artículo
Kidney International 77(6): 509-518 (2010)
0085-2538
http://hdl.handle.net/10261/32423
10.1038/ki.2009.498
eng
http://dx.doi.org/10.1038/ki.2009.498
openAccess
Nature Publishing Group