Our results provide a mechanistic insight into the role of Ha-Ras stabilization in driving collagen I overproduction during the early phase of dermal fibrosis in SSc by showing a direct involvement of the proto-oncogene in stimulating R-Smad signalling independently of TGFβ neo-synthesis or activation and of ERK1/2 signalling. The gene discussed is TGFB1; the disease is systemic sclerosis.