TY - JOUR
T1 - Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures
AU - Kuppe, Christoph
AU - Rohlfs, Wilko
AU - Grepl, Martin
AU - Schulte, Kevin
AU - Veron, Delma
AU - Elger, Marlies
AU - Sanden, Silja Kerstin
AU - Saritas, Turgay
AU - Andrae, Johanna
AU - Betsholtz, Christer
AU - Trautwein, Christian
AU - Hausmann, Ralf
AU - Quaggin, Susan
AU - Bachmann, Sebastian
AU - Kriz, Wilhelm
AU - Tufro, Alda
AU - Floege, Jürgen
AU - Moeller, Marcus J.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Background: Vascular endothelial growth factor A (VEGF) is an essential growth factor during glomerular development and postnatal homeostasis. VEGF is secreted in high amounts by podocytes into the primary urine, back-filtered across the glomerular capillary wall to act on endothelial cells. So far it has been assumed that VEGF back-filtration is driven at a constant rate exclusively by diffusion. Methods: In the present work, glomerular VEGF back-filtration was investigated in vivo using a novel extended model based on endothelial fenestrations as surrogate marker for local VEGF concentrations. Single nephron glomerular filtration rate (SNGFR) and/or local filtration flux were manipulated by partial renal mass ablation, tubular ablation, and in transgenic mouse models of systemic or podocytic VEGF overexpression or reduction. Results: Our study shows positive correlations between VEGF back-filtration and SNGFR as well as effective filtration rate under physiological conditions along individual glomerular capillaries in rodents and humans. Conclusion: Our results suggest that an additional force drives VEGF back-filtration, potentially regulated by SNGFR.
AB - Background: Vascular endothelial growth factor A (VEGF) is an essential growth factor during glomerular development and postnatal homeostasis. VEGF is secreted in high amounts by podocytes into the primary urine, back-filtered across the glomerular capillary wall to act on endothelial cells. So far it has been assumed that VEGF back-filtration is driven at a constant rate exclusively by diffusion. Methods: In the present work, glomerular VEGF back-filtration was investigated in vivo using a novel extended model based on endothelial fenestrations as surrogate marker for local VEGF concentrations. Single nephron glomerular filtration rate (SNGFR) and/or local filtration flux were manipulated by partial renal mass ablation, tubular ablation, and in transgenic mouse models of systemic or podocytic VEGF overexpression or reduction. Results: Our study shows positive correlations between VEGF back-filtration and SNGFR as well as effective filtration rate under physiological conditions along individual glomerular capillaries in rodents and humans. Conclusion: Our results suggest that an additional force drives VEGF back-filtration, potentially regulated by SNGFR.
KW - n/a OA procedure
UR - http://www.scopus.com/inward/record.url?scp=85061474328&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfy057
DO - 10.1093/ndt/gfy057
M3 - Article
C2 - 29635428
AN - SCOPUS:85061474328
SN - 0931-0509
VL - 33
SP - 1514
EP - 1525
JO - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
IS - 9
ER -