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Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development.

Publication ,  Journal Article
Tinning, AR; Jensen, BL; Johnsen, I; Chen, D; Coffman, TM; Madsen, K
Published in: Am J Physiol Renal Physiol
September 1, 2016

Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation. In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg(-1)·day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria. Stereological quantification showed a significant reduction in total length (386 ± 13 vs. 219 ± 16 m), surface area, and volume of medullary microvessels. Vascular bundle architecture was unaffected. ANG II-AT1A/1B (-/-) mice kidneys displayed poorly defined vasa recta bundles whereas mice with collecting duct principal cell-specific AT1A deletion displayed no medullary microvascular phenotype. In conclusion, VEGFR2 signaling during postnatal development is necessary for expansion of the renal medullary microcirculation but not structural patterning of the vasa recta bundles, which occurs through an AT1-mediated mechanism.

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Published In

Am J Physiol Renal Physiol

DOI

EISSN

1522-1466

Publication Date

September 1, 2016

Volume

311

Issue

3

Start / End Page

F586 / F599

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Urology & Nephrology
  • Signal Transduction
  • Receptors, Vascular Endothelial Growth Factor
  • Receptor, Angiotensin, Type 1
  • Rats, Sprague-Dawley
  • Rats
  • Quinazolines
  • Piperidines
  • Microvessels
 

Citation

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Tinning, A. R., Jensen, B. L., Johnsen, I., Chen, D., Coffman, T. M., & Madsen, K. (2016). Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development. Am J Physiol Renal Physiol, 311(3), F586–F599. https://doi.org/10.1152/ajprenal.00221.2016
Tinning, Anne R., Boye L. Jensen, Iben Johnsen, Daian Chen, Thomas M. Coffman, and Kirsten Madsen. “Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development.Am J Physiol Renal Physiol 311, no. 3 (September 1, 2016): F586–99. https://doi.org/10.1152/ajprenal.00221.2016.
Tinning AR, Jensen BL, Johnsen I, Chen D, Coffman TM, Madsen K. Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development. Am J Physiol Renal Physiol. 2016 Sep 1;311(3):F586–99.
Tinning, Anne R., et al. “Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development.Am J Physiol Renal Physiol, vol. 311, no. 3, Sept. 2016, pp. F586–99. Pubmed, doi:10.1152/ajprenal.00221.2016.
Tinning AR, Jensen BL, Johnsen I, Chen D, Coffman TM, Madsen K. Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development. Am J Physiol Renal Physiol. 2016 Sep 1;311(3):F586–F599.

Published In

Am J Physiol Renal Physiol

DOI

EISSN

1522-1466

Publication Date

September 1, 2016

Volume

311

Issue

3

Start / End Page

F586 / F599

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Urology & Nephrology
  • Signal Transduction
  • Receptors, Vascular Endothelial Growth Factor
  • Receptor, Angiotensin, Type 1
  • Rats, Sprague-Dawley
  • Rats
  • Quinazolines
  • Piperidines
  • Microvessels