Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis

フォーマット:

論文

責任表示:

Yamahana, Junya ; Wada, Takashi ; Furuichi, Kengo ; Yokoyama, Hitoshi ; Kaneko, Shuichi

言語:

英語

出版情報:

Blackwell Publishing Inc., 2006-06-01

著者名:

• Yamahana, Junya
• Wada, Takashi
• Furuichi, Kengo
• Yokoyama, Hitoshi
• Kaneko, Shuichi

掲載情報:

Kidney International

ISSN:

0085-2538      

巻:

69

通号:

11

開始ページ:

1986

終了ページ:

1995

バージョン:

author

概要:

金沢大学医学部附属病院血液浄化療法部<br />Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that maintains the glomerular and peritubular capillary (PTC) network in the kidney. The soluble form of the VEGF receptor-1 (soluble fms- … like tyrosine kinase 1 (sFlt-1)) is known to regulate VEGF activity by binding VEGF in the circulation. We hypothesized that VEGF may be beneficial for maintaining glomerular filtration barrier and vascular network in rats with progressive glomerulonephritis (GN). For blockade of VEGF activity in vivo, rats were transfected twice with plasmid DNA encoding the murine sFlt-1 gene into femoral muscle 3 days before and 2 weeks after the induction of antiglomerular basement membrane antibody-induced GN. Inhibition of VEGF with sFlt-1 resulted in massive urinary protein excretion, concomitantly with downregulated expression of nephrin in nephritic rats. Further, blockade of VEGF induced mild proteinuria in normal rats. Administration of sFlt-1 affected neither the infiltration of macrophages nor crescentic formation. In contrast, treatment of sFlt-1 accelerated the progression of glomerulosclerosis and interstitial fibrosis accompanied with renal dysfunction and PTC loss at day 56. VEGF may play a role in maintaining the podocyte function as well as renal vasculature, thereby protecting glomeruli and interstitium from progressive renal insults. ﾂｩ 2006 International Society of Nephrology. 続きを見る

URL:

http://hdl.handle.net/2297/2861