VEGF-A loss in the haematopoietic and endothelial lineages exacerbates age-induced renal changes |
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| Institution: | 1. Department of Urology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China;2. Department of Urology, An Hui Provincial Hospital, 17 Lu Jiang Road, Hefei, Anhui 230001, China;1. Mestrado em Bioquímica em Saúde, Escola Superior de Saúde, Instituto Politécnico do Porto, Porto, Portugal;2. Ciências Químicas e das Biomoléculas, Centro de Investigação em Saúde e Ambiente, Escola Superior de Saúde, Instituto Politécnico do Porto, Portugal;3. I3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;4. Departamento de Bioquímica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal;1. Orthopedic Department, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China;2. Guangdong Provincial Key Laboratory of Orthopedics and Traumatology/Orthopedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510075, China;3. Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China;4. School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, China;5. National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China;6. Department of Burn Surgery and Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330000, China |
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| 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. |
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