VEGF induces proliferation, migration, and TGF-beta1 expression in mouse glomerular endothelial cells via mitogen-activated protein kinase and phosphatidylinositol 3-kinase.
Biochem Biophys Res Commun
; 334(4): 1049-60, 2005 Sep 09.
Article
em En
| MEDLINE
| ID: mdl-16039615
ABSTRACT
The role of glomerular endothelial cells in kidney fibrosis remains incompletely understood. While endothelia are indispensable for repair of acute damage, they can produce extracellular matrix proteins and profibrogenic cytokines that promote fibrogenesis. We used a murine cell line with all features of glomerular endothelial cells (glEND.2), which dissected the effects of vascular endothelial growth factor (VEGF) on cell migration, proliferation, and profibrogenic cytokine production. VEGF dose-dependently induced glEND.2 cell migration and proliferation, accompanied by up-regulation of VEGFR-2 phosphorylation and mRNA expression. VEGF induced a profibrogenic gene expression profile, including up-regulation of TGF-beta1 mRNA, enhanced TGF-beta1 secretion, and bioactivity. VEGF-induced endothelial cell migration and TGF-beta1 induction were mediated by the phosphatidyl-inositol-3 kinase pathway, while proliferation was dependent on the Erk1/2 MAP kinase pathway. This suggests that differential modulation of glomerular angiogenesis by selective inhibition of the two identified VEGF-induced signaling pathways could be a therapeutic approach to treat kidney fibrosis.
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Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Fator de Crescimento Transformador beta
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Fosfatidilinositol 3-Quinases
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Proteínas Quinases Ativadas por Mitógeno
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Células Endoteliais
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Fator A de Crescimento do Endotélio Vascular
/
Glomérulos Renais
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article