Journal of the American Society of Nephrology
2007 JASN IMPACT FACTOR 7.111 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by TUFRO, A.
Right arrow Articles by GOMEZ, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by TUFRO, A.
Right arrow Articles by GOMEZ, R. A.
J Am Soc Nephrol 10:2125-2134, 1999
© 1999 American Society of Nephrology

Vascular Endothelial Growth Factor Induces Nephrogenesis and Vasculogenesis

ALDA TUFRO*, VICTORIA F. NORWOOD*, ROBERT M. CAREY{dagger} and R. ARIEL GOMEZ*

* Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia.
{dagger} Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia.

Correspondence to Dr. Alda Tufro, Department of Pediatrics/Nephrology, University of Virginia, MR4 Bldg./Room 2017, Charlottesville, VA 22908. Phone: 804-982-4388; Fax: 804-982-4328; E-mail: at4w{at}virginia.edu

Abstract. The expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in the rat kidney was examined during ontogeny using Northern blot analysis and immunocytochemistry. In prevascular embryonic kidneys (embryonic day 14 [E14]), immunoreactive Flt-1 and Flk-1 were observed in isolated angioblasts, whereas VEGF was not detected. Angioblasts aligned forming cords before morphologically differentiating into endothelial cells. In late fetal kidneys (E19), immunoreactive VEGF was detected in glomerular epithelial and tubular cells, whereas Flt-1 and Flk-1 were expressed in contiguous endothelial cells. To determine whether VEGF induces endothelial cell differentiation and vascular development in the kidney, the effect of recombinant human VEGF (5 ng/ml) was examined on rat metanephric organ culture, a model known to recapitulate nephrogenesis in the absence of vessels. After 6 d in culture in serum-free, defined media, metanephric kidney growth and morphology were assessed. DNA content was higher in VEGF-treated explants (1.9 ± 0.17 µg/kidney, n = 9) than in paired control explants (1.4 ± 0.10 µg/kidney, n = 9) (P < 0.05). VEGF induced proliferation of tubular epithelial cells, as indicated by an increased number of tubules and tubular proliferating cell nuclear antigen-containing cells. VEGF induced upregulation of Flk-1 and Flt-1 expression, as assessed by Western blot analysis. Developing endothelial cells were identified and localized using immunocytochemistry and electron microscopy. Flt-1, Flk-1, and angiotensin-converting enzyme-containing cells were detected in VEGF-treated explants, whereas control explants were negative. These studies confirmed previous reports indicating that the expression of VEGF and its receptors is temporally and spatially associated with kidney vascularization and identified angioblasts expressing Flt-1 and Flk-1 in prevascular embryonic kidneys. The data indicate that VEGF expression is downregulated in standard culture conditions and that VEGF stimulates growth of embryonic kidney explants by expanding both endothelium and epithelium, resulting in vasculogenesis and enhanced tubulogenesis. These data suggest that VEGF plays a critical role in renal development by promoting endothelial cell differentiation, capillary formation, and proliferation of tubular epithelia.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
V. Campean, B. Karpe, C. Haas, A. Atalla, H. Peters, H. Rupprecht, S. Liebner, T. Acker, K. Plate, and K. Amann
Angiopoietin 1 and 2 gene and protein expression is differentially regulated in acute anti-Thy1.1 glomerulonephritis
Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1174 - F1184.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
L. E. Burt, M. S. Forbes, B. A. Thornhill, S. C. Kiley, and R. L. Chevalier
Renal vascular endothelial growth factor in neonatal obstructive nephropathy. I. Endogenous VEGF
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F158 - F167.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
L. E. Burt, M. S. Forbes, B. A. Thornhill, S. C. Kiley, J. J. Minor, and R. L. Chevalier
Renal vascular endothelial growth factor in neonatal obstructive nephropathy. II. Exogenous VEGF
Am J Physiol Renal Physiol, January 1, 2007; 292(1): F168 - F174.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
F. Guan, G. Villegas, J. Teichman, P. Mundel, and A. Tufro
Autocrine VEGF-A system in podocytes regulates podocin and its interaction with CD2AP
Am J Physiol Renal Physiol, August 1, 2006; 291(2): F422 - F428.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. E.J. Reinders, T. J. Rabelink, and D. M. Briscoe
Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection
J. Am. Soc. Nephrol., April 1, 2006; 17(4): 932 - 942.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
X. Gao, X. Chen, M. Taglienti, B. Rumballe, M. H. Little, and J. A. Kreidberg
Angioblast-mesenchyme induction of early kidney development is mediated by Wt1 and Vegfa
Development, December 15, 2005; 132(24): 5437 - 5449.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Karihaloo, S. A. Karumanchi, W. L. Cantley, S. Venkatesha, L. G. Cantley, and S. Kale
Vascular Endothelial Growth Factor Induces Branching Morphogenesis/Tubulogenesis in Renal Epithelial Cells in a Neuropilin-Dependent Fashion
Mol. Cell. Biol., September 1, 2005; 25(17): 7441 - 7448.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
B. M. Steenhard, K. S. Isom, P. Cazcarro, J. H. Dunmore, A. R. Godwin, P. L. St. John, and D. R. Abrahamson
Integration of Embryonic Stem Cells in Metanephric Kidney Organ Culture
J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1623 - 1631.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
P. H. Lapchak, M. Melter, S. Pal, J. A. Flaxenburg, C. Geehan, M. H. Frank, D. Mukhopadhyay, and D. M. Briscoe
CD40-induced transcriptional activation of vascular endothelial growth factor involves a 68-bp region of the promoter containing a CpG island
Am J Physiol Renal Physiol, September 1, 2004; 287(3): F512 - F520.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
J. M. Ricono, Y.-C. Xu, M. Arar, D.-c. Jin, J. L. Barnes, and H. E. Abboud
Morphological Insights into the Origin of Glomerular Endothelial and Mesangial Cells and Their Precursors
J. Histochem. Cytochem., February 1, 2003; 51(2): 141 - 150.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
H. Pavenstadt, W. Kriz, and M. Kretzler
Cell Biology of the Glomerular Podocyte
Physiol Rev, January 1, 2003; 83(1): 253 - 307.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. A. Oliver, J. Barasch, J. Yang, D. Herzlinger, and Q. Al-Awqati
Metanephric mesenchyme contains embryonic renal stem cells
Am J Physiol Renal Physiol, October 1, 2002; 283(4): F799 - F809.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
R. Ohashi, A. Shimizu, Y. Masuda, H. Kitamura, M. Ishizaki, Y. Sugisaki, and N. Yamanaka
Peritubular Capillary Regression during the Progression of Experimental Obstructive Nephropathy
J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1795 - 1805.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
V. Mattot, L. Moons, F. Lupu, D. Chernavvsky, R. A. Gomez, D. Collen, and P. Carmeliet
Loss of the VEGF164 and VEGF188 Isoforms Impairs Postnatal Glomerular Angiogenesis and Renal Arteriogenesis in Mice
J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1548 - 1560.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
T. Takahashi, K. Takahashi, S. Gerety, H. Wang, D. J. Anderson, and T. O. Daniel
Temporally Compartmentalized Expression of Ephrin-B2 during Renal Glomerular Development
J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2673 - 2682.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. R. S. Brown, K. M. England, K. L. Goss, J. M. Snyder, and M. J. Acarregui
VEGF induces airway epithelial cell proliferation in human fetal lung in vitro
Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L1001 - L1010.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. L. S. Sequeira Lopez, E. S. Pentz, B. Robert, D. R. Abrahamson, and R. A. Gomez
Embryonic origin and lineage of juxtaglomerular cells
Am J Physiol Renal Physiol, August 1, 2001; 281(2): F345 - F356.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. Dunk and A. Ahmed
Vascular Endothelial Growth Factor Receptor-2-Mediated Mitogenesis Is Negatively Regulated by Vascular Endothelial Growth Factor Receptor-1 in Tumor Epithelial Cells
Am. J. Pathol., January 1, 2001; 158(1): 265 - 273.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
B. Robert, X. Zhao, and D. R. Abrahamson
Coexpression of neuropilin-1, Flk1, and VEGF164 in developing and mature mouse kidney glomeruli
Am J Physiol Renal Physiol, August 1, 2000; 279(2): F275 - F282.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. Kanellis, S. Fraser, M. Katerelos, and D. A. Power
Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells
Am J Physiol Renal Physiol, June 1, 2000; 278(6): F905 - F915.
[Abstract] [Full Text] [PDF]


HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673