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Open Access item Deletion of H-Ras decreases renal fibrosis and myofibroblast activation following ureteral obstruction in mice

Authors: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.
Keywords:Cell biology and structure, Extracellular matrix, Fibroblast, Interstitial fibrosis, Obstructive nephropathy
Issue Date:Mar-2010
Publisher:Nature Publishing Group
Citation:Kidney International 77(6): 509-518 (2010)
Abstract: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.
Description:10 páginas.
Publisher version (URL):http://dx.doi.org/10.1038/ki.2009.498
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