Open AccessVEGF receptors and neuropilins are expressed in the urothelial and neuronal cells in normal mouse urinary bladder and are upregulated in inflammation
Author(s) -
Marcia R. Saban,
Joseph M. Backer,
Marina V. Backer,
Julie Maier,
Ben Fowler,
Carole Davis,
Cindy Simpson,
Xue-Ru Wu,
Lori Birder,
Michael R. Freeman,
Shay Söker,
Robert E. Hurst,
Ricardo Saban
Publication year - 2008
Publication title -
american journal of physiology. renal physiology./american journal of physiology. renal physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.335
H-Index - 169
eISSN - 1931-857X
pISSN - 1522-1466
DOI - 10.1152/ajprenal.00618.2007
Subject(s) - inflammation , neuropilin 1 , cancer research , downregulation and upregulation , urothelial cell , in vivo , urinary bladder , receptor , vascular endothelial growth factor , urothelium , ex vivo , kinase insert domain receptor , chemistry , pathology , biology , vascular endothelial growth factor a , vegf receptors , medicine , immunology , gene , biochemistry , microbiology and biotechnology
Recent evidence supports a role for vascular endothelium growth factor (VEGF) signaling in bladder inflammation. However, it is not clear what bladder cells are targeted by VEGF. Therefore, we determined the nature of cells responding to VEGF in normal and inflamed bladders by tagging such cells in vivo with a targeted fluorescent tracer, scVEGF/Cy, an engineered single-chain VEGF labeled with Cy5.5 dye, which identifies cells with accessible and functionally active VEGF receptors. Inflammation was induced by intravesical instillation of PAR-activating peptides or BCG. In vivo NIRF imaging with intravenously injected scVEGF/Cy revealed accumulation of the tracer in the control mouse bladder and established that inflammation increased the steady-state levels of tracer uptake. Ex vivo colocalization of Cy5.5 dye revealed that in normal and at a higher level in inflamed bladder, accumulation of scVEGF/Cy occurs in both urothelial and ganglial cells, expressing VEGF receptors VEGFR-1 and VEGFR-2, as well as VEGF coreceptors neuropilins (NRP) NRP1 and NRP2. PCR results indicate that the messages for VEGF-Rs and NRPs are present in the bladder mucosa and ChIP/QPCR analysis indicated that inflammation induced upregulation of genes encoding VEGFRs and NRPs. Our results strongly suggest new and blossoming VEGF-driven processes in bladder urothelial cells and ganglia in the course of inflammation. We expect that molecular imaging of the VEGF pathway in the urinary tract by receptor-mediated cell tagging in vivo will be useful for clinical diagnosis and therapeutic monitoring, and will help to accelerate the development of bladder-targeting drugs and treatments.