VEGF-A loss in the haematopoietic and endothelial lineages exacerbates age-induced renal changes.
Microvasc Res
; 80(3): 372-83, 2010 Dec.
Article
in En
| MEDLINE
| ID: mdl-20659482
ABSTRACT
Renal function declines with age and this is more pronounced in males than females. VEGF-A is essential for glomerular development and function but its role in other aspects of renal function is poorly understood. We therefore investigated the role of VEGF-A, derived specifically from haematopoietic and endothelial lineages in the kidney. We crossed VavCre and floxed Vegf-a mice allowing specific ablation of a single Vegf-a allele in the haematopoietic and endothelial lineages. Mutants were viable and fertile and had normal haematological composition, indicating that 50% gene dosage of Vegf-a in the Vav-expressing lineage is sufficient for establishing a functional haematopoietic system and mature vascular network. However, several abnormalities were observed in the kidney of the adult mutants. These included the formation of inclusion bodies in the proximal tubular cells, tubular atrophy and interstitial fibrosis. These features were observed in 9-11 month-old mutant animals. Most of these abnormalities have been described in aging kidneys in man, and were also observed in the older control mice (24 months). The pathological features appeared in mutant male animals at a younger age than in female mutants. This indicates that reduction in Vegf-a gene dosage in haematopoietic and endothelial lineages accelerates renal aging, suggesting that VEGF-A derived from these lineages may play a role in protecting the kidney from age-associated damage.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Hematopoietic Stem Cells
/
Cell Lineage
/
Endothelial Cells
/
Vascular Endothelial Growth Factor A
/
Kidney
Limits:
Animals
Language:
En
Journal:
Microvasc Res
Year:
2010
Document type:
Article
Affiliation country:
Reino Unido
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA