Renal vascular endothelial growth factor in neonatal obstructive nephropathy. I. Endogenous VEGF

• Published in: American journal of physiology. Renal physiology Vol. 292; no. 1; pp. F158 - F167
• Main Authors: Burt, Laura E, Forbes, Michael S, Thornhill, Barbara A, Kiley, Susan C, Chevalier, Robert L
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2007
• Subjects: Animals; Animals, Newborn - physiology; Apoptosis; Blotting, Western; Glyceraldehyde-3-Phosphate Dehydrogenases - biosynthesis; Glyceraldehyde-3-Phosphate Dehydrogenases - genetics; Immunohistochemistry; Kidney - metabolism; Kidney - pathology; Kidney Cortex - metabolism; Kidney Diseases - etiology; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidney Medulla - metabolism; Kidney Tubules, Collecting - metabolism; Kidneys; Maturation; Proton-Translocating ATPases - metabolism; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Rodents; Ureteral Obstruction - complications; Ureteral Obstruction - metabolism; Ureteral Obstruction - pathology; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - biosynthesis; Vascular Endothelial Growth Factor Receptor-2 - genetics
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00293.2005

Obstructive nephropathy constitutes a major cause of renal impairment in children. Chronic unilateral ureteral obstruction (UUO) impairs maturation of the developing kidney and leads to tubular apoptosis and interstitial inflammation. Vascular endothelial growth factor (VEGF) is involved in recovery from various forms of renal injury. We questioned whether the renal expression of endogenous VEGF and its receptor (VEGFR2/Flk-1) is modified by UUO in early development. Neonatal rats were subjected to partial or complete UUO or sham operation. The distribution of immunoreactive VEGF in each kidney was examined after 7, 14, or 28 days. Adult rats were also subjected to sham operation or complete UUO. Tubular VEGF increased between 14 and 28 days in sham-operated rats and in some partially obstructed neonatal rats but decreased with complete UUO. Parallel changes were found by Western blotting, but not by RT-PCR. Immunoreactive VEGF colocalized with mitochondria in proximal and distal tubules and also appeared in type A intercalated cells, glomerular vascular endothelium, and podocytes. While neonatal microvascular renal VEGFR2 receptor staining was strongly positive regardless of UUO, staining was weak in sham-operated adults but increased following UUO. Parallel changes in VEGFR2 expression were verified by RT-PCR and Western blotting. We conclude that endogenous renal VEGF is developmentally regulated in the neonatal rat and is differentially regulated by partial and complete UUO. Following UUO in the adult, the VEGF receptor is upregulated. Endogenous VEGF may serve an adaptive role in responding to tubular injury caused by UUO and may modulate adaptation by the contralateral kidney.