Christoph Kuppe1, Wilko Rohlfs2, Martin Grepl3, Kevin Schulte1,4, Delma Veron5, Marlies Elger6, Silja Kerstin Sanden1, Turgay Saritas1, Johanna Andrae7, Christer Betsholtz7, Christian Trautwein8, Ralf Hausmann9, Susan Quaggin10, Sebastian Bachmann11, Wilhelm Kriz6, Alda Tufro5, Jürgen Floege1, Marcus J Moeller1,12,13. 1. Division of Nephrology and Immunology, RWTH Aachen University, Aachen, Germany. 2. Institute of Heat and Mass Transfer, RWTH Aachen University, Aachen, Germany. 3. Numerical Mathematics, Faculty for Mathematics, Informatics and Natural Sciences, RWTH Aachen University, Aachen, Germany. 4. Department of Nephrology, University of Kiel, Kiel, Germany. 5. Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA. 6. Department of Anatomy and Developmental Biology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. 7. Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden. 8. Division of Gastroenterology and Endocrinology, RWTH Aachen University Hospital, Aachen, Germany. 9. Institute of Molecular Pharmacology, RWTH Aachen University Hospital, Aachen, Germany. 10. Division of Medicine-Nephrology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 11. Department of Anatomy, Charité Universitätsmedizin, Berlin, Germany. 12. Interdisciplinary Centre for Clinical Research (IZKF Aachen), RWTH Aachen University Hospital, Aachen, Germany. 13. Heisenberg Chair for Preventive and Translational Nephrology, Division of Nephrology, RWTH Aachen University, Aachen, Germany.
Abstract
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.
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.
Authors: Ralf Hausmann; Christoph Kuppe; Herbert Egger; Frank Schweda; Volker Knecht; Marlies Elger; Sylvia Menzel; Douglas Somers; Gerald Braun; Astrid Fuss; Sandra Uhlig; Wilhelm Kriz; George Tanner; Jürgen Floege; Marcus J Moeller Journal: J Am Soc Nephrol Date: 2010-10-14 Impact factor: 10.121
Authors: Nicholas Ferrell; Kathleen O Cameron; Joseph J Groszek; Christina L Hofmann; Lingyan Li; Ross A Smith; Aihua Bian; Ayumi Shintani; Andrew L Zydney; William H Fissell Journal: Biophys J Date: 2013-04-02 Impact factor: 4.033
Authors: Delma Veron; Kimberly J Reidy; Claudia Bertuccio; Jason Teichman; Guillermo Villegas; Juan Jimenez; Wa Shen; Jeffrey B Kopp; David B Thomas; Alda Tufro Journal: Kidney Int Date: 2010-03-10 Impact factor: 10.612
Authors: Kevin Schulte; Katja Berger; Peter Boor; Peggy Jirak; Irwin H Gelman; Kenton P Arkill; Christopher R Neal; Wilhelm Kriz; Jürgen Floege; Bart Smeets; Marcus J Moeller Journal: J Am Soc Nephrol Date: 2013-09-26 Impact factor: 10.121
Authors: Lionel C Clement; Carmen Avila-Casado; Camille Macé; Elizabeth Soria; Winston W Bakker; Sander Kersten; Sumant S Chugh Journal: Nat Med Date: 2010-12-12 Impact factor: 53.440
Authors: Marcus J Moeller; Rafael Kramann; Twan Lammers; Bernd Hoppe; Eicke Latz; Isis Ludwig-Portugall; Peter Boor; Jürgen Floege; Christian Kurts; Ralf Weiskirchen; Tammo Ostendorf Journal: Front Med (Lausanne) Date: 2022-01-12