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Acta Physiologica 2007; Volume 190, Supplement 655
XXXIV Congress of The Spanish Society for Physiological Sciences
7/3/2007-7/7/2007
Valladolid, Spain
H- AND N-RAS ISOFORMS MODULATES DIFFERENTIALLY EXTRACELLULAR MATRIX SYNTHESIS AND PROLIFERATION INDUCED BY TRANSFORMING GROWTH FACTOR-BETA 1
Abstract number: P11
Fuentes-Calvo I, Blazquez-Medela AM, Garcia-Cenador B, Santos1 E, Lopez-Novoa JM, Martinez-Salgado2 C.
1Centro de Investigacin del Cncer, Salamanca, Spain
2Unidad de Investigacin, Hospital Universitario de Salamanca
Transforming growth factor beta 1 (TGF-beta 1) regulates cell proliferation and renal extracellular matrix (ECM) synthesis and degradation, having a relevant role in the origin and maintenance of glomerulosclerosis and tubule-interstitial fibrosis. It is well known that TGF-beta and Ras signalling pathways are closely related. Ras proteins are GTPases that act as transducers of extracellular signals; there are 3 main Ras isoforms: H, N and K-Ras. We assessed the individual role of H- and N-Ras isoforms in TGF-beta 1-mediated ECM synthesis and proliferation, analyzing embrionary fibroblasts obtained from mice knockout for H-Ras (H-ras-/-) and N-Ras (N-ras-/-) isoforms. ECM synthesis was studied by evaluating fibronectin and collagen type I expression by western blot and total collagen synthesis by [3H]-proline uptake into collagen proteins. Fibroblast proliferation was measured by crystal violet nuclei staining.
Fibronectin and collagen type I expression, and total collagen synthesis, is higher in N-ras-/- than in control N-ras+/+ fibroblasts, both in basal conditions and after TGF-beta 1 treatment; the lack of H-Ras isoform induced only a small increase in the expression of collagen type I and fibronectin with respect to control fibroblasts, either with or without TGF-beta 1 treatment. TGF-beta 1-induced fibroblast proliferation is reduced in H-ras-/- with respect to H-ras+/+ fibroblasts, whereas the absence of N-Ras did not induce any difference in fibroblast proliferation. Our data suggest that N-Ras isoform seems to down-regulate fibronectin and collagen synthesis; on the other hand, H-Ras mediates the TGF-beta 1-induced proliferation in fibroblast, with a less important effect in ECM synthesis
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Acta Physiologica 2007; Volume 190, Supplement 655 :P11