Essential role of Gas6 for glomerular injury in nephrotoxic nephritis
AUTOR(ES)
Yanagita, Motoko
FONTE
American Society for Clinical Investigation
RESUMO
Growth-arrest specific gene 6 (Gas6) is a vitamin K–dependent growth factor for mesangial and epithelial cells. To investigate whether Gas6 is essential for progressive glomerular injury, we constructed Gas6–/– mice and examined the role of Gas6 in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis. We found less mortality and proteinuria in Gas6–/– mice than in wild-type mice following injection of nephrotoxic serum. Glomerular cell proliferation, glomerular sclerosis, crescent formation, and deposition of fibrin/fibrinogen in glomeruli were also reduced in Gas6–/– mice. Furthermore, administering Gas6–/– mice recombinant wild-type Gas6, but not Gas6 lacking a previously characterized N-terminal γ-carboxyl group, induced massive proteinuria, glomerular cell proliferation, and glomerulosclerosis, comparable to responses seen in wild-type mice. These data indicate that Gas6 induces glomerular cell proliferation in NTN and suggest that this factor contributes to glomerular injury and the progression of chronic nephritis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=151046Documentos Relacionados
- Monocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis
- Glomerular arachidonate lipoxygenation in rat nephrotoxic serum nephritis.
- Lack of chemokine receptor CCR1 enhances Th1 responses and glomerular injury during nephrotoxic nephritis
- Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy
- The glomerular mesangium. II. Studies of macromolecular uptake in nephrotoxic nephritis in rats.