In addition to their role as oncogenes, Ras GTPases are key regulators of cell 
function. There is a proven relationship between the signaling pathways of 
transforming growth factor-β1 (TGF- β1) and Ras GTPases. Each of the Ras 
isoforms (H, N and K) exhibits specific modulatory activity on different 
cellular pathways. Our purpose has been to study some of the mechanisms involved 
in the development of renal fibrosis, assessing the individual role of N-Ras in 
basal and TGF-β1-mediated extracellular matrix (ECM) synthesis, proliferation, 
and migration in immortalized N-Ras deficient fibroblasts (N-ras(-/-)). Compared 
to normal counterparts, fibroblasts deficient for N-Ras exhibited higher basal 
activity levels of phosphatidylinositol-3-kinase (PI3K)/Akt and MEK/Erk, 
accompanied by upregulated collagen synthesis and diminished proliferation and 
migration rates. We found that the absence of N-Ras did not affect 
TGF-β1-induced proliferation and migration, which required PI3K/Akt but not 
Erk1/2 activation. Similar effector pathway dependence was found for fibronectin 
and collagen type I expression. Our results indicate that N-Ras might contribute 
to renal fibrosis through the down-regulation of ECM synthesis and up-regulation 
proliferation and migration modulating Akt activation. N-Ras also regulates 
TGF-β1-induced collagen I and fibronectin expression through Erk-independent 
pathways.