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Am J Physiol Renal Physiol 295: F826-F836, 2008. First published July 16, 2008; doi:10.1152/ajprenal.90305.2008
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Upregulation of vascular endothelial growth factor isoform VEGF-164 and receptors (VEGFR-2, Npn-1, and Npn-2) in rats with cyclophosphamide-induced cystitis

Bopaiah P. Cheppudira,1 Beatrice M. Girard,2 Susan E. Malley,1 Kristin C. Schutz,2 Victor May,2 and Margaret A. Vizzard1,2

Departments of 1Neurology and 2Anatomy, University of Vermont College of Medicine, Burlington, Vermont

Submitted 13 May 2008 ; accepted in final form 11 July 2008

Regulation of the VEGF-VEGF receptor system was examined in the urinary bladder after acute (2–48 h) and chronic (10 days) cyclophosphamide (CYP)-induced cystitis. ELISAs demonstrated significant (P ≤ 0.01) upregulation of VEGF in whole urinary bladder with acute and chronic CYP-induced cystitis; however, the magnitude of increase was greater after acute (2–4 h) cystitis. Immunohistochemistry for VEGF immunoreactivity revealed a significant (P ≤ 0.05) increase in VEGF immunoreactivity in the urothelium, suburothelial vasculature, and detrusor smooth muscle with acute (4 and 48 h) CYP treatment. RT-PCR identified the isoform VEGF-164, the VEGF receptor VEGFR-2, and the VEGF co-receptors neuropilin (Npn)-1 and Npn-2 in the urinary bladder. Quantitative PCR demonstrated upregulation of VEGF-164 transcript with acute and chronic CYP-induced cystitis, but VEGFR-2, Npn-1, and Npn-2 transcripts were upregulated (P ≤ 0.01) in whole bladder only with chronic CYP-induced cystitis. Additional studies demonstrated regulation of VEGF transcript expression in the urinary bladder by nerve growth factor (NGF) in a novel line of NGF-overexpressing mice. These studies demonstrated that urinary bladder inflammation and NGF regulate the VEGF-VEGF receptor system in the urinary bladder. Functional role(s) for the VEGF-VEGF receptor system in urinary bladder inflammation remain to be determined.

urothelium; quantitative polymerase chain reaction; immunohistochemistry; detrusor smooth muscle; vasculature; nerve growth factor



Address for reprint requests and other correspondence: M. A. Vizzard, Dept. of Neurology, Univ. of Vermont College of Medicine, D415A Given Research Bldg., Burlington, VT 05405 (e-mail: margaret.vizzard{at}uvm.edu)




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