Renal vascular endothelial growth factor in neonatal obstructive nephropathy. I. Endogenous VEGF
Renal vascular endothelial growth factor in neonatal obstructive nephropathy. I. Endogenous VEGF
复制标题
DOI：
10.1152/ajprenal.00293.2005
复制
发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Chevalier, Robert L.
中科院分区：
文献类型：
--
作者：
Burt, Laura E.;Forbes, Michael S.;Chevalier, Robert L.
梗阻性肾病是儿童肾损害的主要原因。慢性单侧输尿管梗阻（UUO）损害发育中肾脏的成熟，导致肾小管细胞凋亡和间质炎症。血管内皮生长因子（VEGF）参与各种形式的肾损伤的恢复。我们质疑肾脏内源性VEGF及其受体（VEGFR 2/Flk-1）的表达是否在早期发育中被UUO改变。新生大鼠进行部分或完全UUO或假手术。在7、14或28天后检查免疫反应性VEGF在每个肾脏中的分布。成年大鼠也进行假手术或完全UUO。假手术大鼠和部分梗阻新生大鼠肾小管VEGF在14 - 28天之间增加，但在完全UUO时减少。Western blotting检测到了类似的变化，而RT-PCR检测没有发现。免疫反应性VEGF与近端和远端小管的线粒体共定位，也出现在A型闰细胞，肾小球血管内皮细胞和足细胞。尽管新生儿肾微血管VEGFR 2受体染色强阳性，但无论UUO如何，假手术成人中染色较弱，但在UUO后染色增加。RT-PCR和Western blotting证实了VEGFR 2表达的平行变化。我们的结论是内源性肾脏VEGF的发育调节新生大鼠和差异调节部分和完全UUO。在成人UUO后，VEGF受体上调。内源性VEGF可能在UUO引起的肾小管损伤中起适应性作用，并可能通过对侧肾脏调节适应性。
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.