Upregulation of vascular endothelial growth factor isoform VEGF-164 and receptors (VEGFR-2, Npn-1, and Npn-2) in rats with cyclophosphamide-induced cystitis.
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 < or = 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 < or = 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 < or = 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.
Cheppudira
Bopaiah P
BP
Department of Neurology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Girard
Beatrice M
BM
Malley
Susan E
SE
Schutz
Kristin C
KC
May
Victor
V
Vizzard
Margaret A
MA
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics; D009130:Muscle, Smooth / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D039921:Neuropilins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D060170:Uroplakin II; D019459:Urothelium / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D018906:Antineoplastic Agents, Alkylating; D008565:Membrane Proteins; D039921:Neuropilins; D020033:Protein Isoforms; D012333:RNA, Messenger; C554659:Upk2 protein, mouse; D060170:Uroplakin II; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003520:Cyclophosphamide; D020932:Nerve Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2