VEGF receptor inhibition slows the progression of polycystic kidney disease.
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.
Tao
Y
Y
Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA. Yunxia.Tao@TTUHSC.edu
Kim
J
J
Yin
Y
Y
Zafar
I
I
Falk
S
S
He
Z
Z
Faubel
S
S
Schrier
R W
RW
Edelstein
C L
CL
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D006579:Heterozygote; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D007690:Polycystic Kidney Diseases / Q000378:metabolism / Q000473:pathology*; D016337:RNA, Catalytic / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016337:RNA, Catalytic; D012333:RNA, Messenger; D040262:Receptors, Vascular Endothelial Growth Factor