VEGF receptor inhibition slows the progression of polycystic kidney disease
VEGF receptor inhibition slows the progression of polycystic kidney disease
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DOI：
10.1038/sj.ki.5002550
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发表时间：
2007-12-01
影响因子：
19.6
通讯作者：
Edelstein, C. L.
中科院分区：
文献类型：
--
作者：
Tao, Y.;Kim, J.;Edelstein, C. L.
虽然血管内皮生长因子（VEGF）的受体通过位于内皮细胞上的受体发挥其对血管发生和血管生成的作用，但最近的研究表明这些受体也存在于肾小管上皮细胞上。我们研究了VEGF在Han：SPRD杂合子（Cy/+）多囊肾病大鼠模型中对肾小管细胞增殖增加的作用。Cy/+大鼠肾脏和血清中VEGF水平以及肾小管上两种受体的表达均增加。这些大鼠被给予特异性抑制VEGFR 1和VEGFR 2 mRNA表达的核酶。在核酶处理的动物中，囊肿内的小管细胞增殖显著降低，导致囊肿形成减少，肾肿大变钝，并防止肾功能丧失。我们的研究表明，抑制VEGF功能可能是延缓多囊肾疾病进展的重要治疗选择。
Although the receptors for vascular endothelial growth factor (VEGF) exert their effects on vasculogenesis and angiogenesis through receptors located on endothelial cells, recent studies have shown that these receptors are also present on renal tubular epithelial cells. We investigated the role of VEGF on increased tubule cell proliferation in the Han: SPRD heterozygous (Cy/+) rat model of polycystic kidney disease. The levels of VEGF in the kidneys and the serum, and the expression of the two receptors on tubules were increased in Cy/+ rats. These rats were given ribozymes that specifically inhibited VEGFR1 and VEGFR2 mRNA expression. Tubule cell proliferation within the cysts was significantly decreased in the ribozyme-treated animals leading to decreased cystogenesis, blunted renal enlargement, and prevented the loss of renal function. Our studies show that inhibition of VEGF function may be an important therapeutic option to delay the progression of polycystic kidney disease.