Forced expression of vascular endothelial growth factor-A in podocytes decreases mesangial cell numbers and attenuates endothelial cell differentiation in the mouse glomerulus.
Clin Exp Nephrol
; 22(2): 266-274, 2018 Apr.
Article
en En
| MEDLINE
| ID: mdl-28776225
ABSTRACT
BACKGROUND:
Glomerular podocyte-derived vascular endothelial growth factor (VEGF) is indispensable for the migration and proliferation of glomerular endothelial cells. In contrast, podocyte-specific Vegf overexpression leads to the collapse of glomerular tufts; however, the mechanisms underlying this outcome have not yet been reported.METHODS:
To further clarify the effects of elevated levels of Vegf expression on glomerular cells, we established a dual transgenic mouse line in which Vegf was exclusively and inducibly expressed in podocytes under the control of the "Tet-on system" (Podocin-rtTA/TetO-Vegf164 mice).RESULTS:
Macroscopic and microscopic examination of Podocin-rtTA/TetO-Vegf164 animals following Vegf induction identified the presence of prominent red bloody spots. In addition, the endothelial cell number was increased along with enlargement of the subendothelial spaces. We also observed impaired endothelial fenestrations and aberrant plasmalemmal vesicle-associated protein-1 (PV-1) expression. In contrast, the mesangial cell number markedly decreased, resulting in a glomerular tuft intussusceptive splitting defect. Furthermore, whereas platelet-derived growth factor-B (PDGF-B) expression in the glomerular cells of Podocin-rtTA/TetO-Vegf164 mice was not decreased, phospho-PDGF receptor immunoreactivity in the mesangial cells was significantly decreased when compared to wild-type animals.CONCLUSION:
Taken together, the results of this study indicated that the upregulation of podocyte VEGF decreased the number of mesangial cells, likely owing to inhibition of PDGF-B-mediated signaling.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Células Endoteliales
/
Factor A de Crecimiento Endotelial Vascular
/
Células Mesangiales
/
Podocitos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Nephrol
Asunto de la revista:
NEFROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón