Involvement of small Ras GTPases and their effectors in chronic renal disease.
The mechanisms involved in the development of renal fibrosis are poorly understood. Small Ras GTPases control cell proliferation, differentiation, cellular growth and apoptosis, with cell-specific expression in the kidney. Cytokines, high glucose medium or advanced glycation end-products activate Ras in different renal cells. Increased Ras activation has been found in experimental tubulointerstitial fibrosis. Transforming growth factor-beta1 (TGF-beta1) and Ras signalling pathways are close related: TGF-beta1 overcomes Ras mitogenic effects, and Ras counteracts TGF-beta signalling. However, Ras activation is also an intracellular signal transduction point for several molecules (e.g. TGF-beta1) involved in kidney damage. Ras isoforms play different roles in regulating extracellular matrix synthesis in fibroblasts and mesangial cells. These data give evidence for a role for Ras in renal fibrosis, but no reviews are available on the role of p21 Ras in this process. Thus, our goal is to review the role of Ras activation and signalling in renal fibrosis.
Martínez-Salgado
C
C
Unidad de Investigación, Hospital Universitario de Salamanca, Salamanca, Spain.
Rodríguez-Peña
A B
AB
López-Novoa
J M
JM
D049109:Cell Proliferation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D020033:Protein Isoforms; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins