Urothelial Expression Of Neuropilins And VEGF Receptors In Control And Interstitial Cystitis Patients

Main Category: Urology / Nephrology
Article Date: 14 Jan 2009 - 6:00 PDT

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UroToday.com - One theory for the cause of urothelial dysfunction in BPS/IC is that antiproliferative factor, a frizzled 8-derived sialoglycopeptide produced by cells derived from BPS patients, increases the permeability of the bladder. Another putative candidate is vascular endothelial growth factor (VGEF). VEGF has been most intensively studied with respect to its actions on vascular cells. In the bladder, increased staining of VEGF was reported in patients with glomerulations on hydrodistention, but not in patients who failed to show petechial bleeding or in controls.

Dr. Ricardo Saban and colleagues from the University of Oklahoma have shown that VEGF appears to be active in the urothelial cells in addition to vascular endothelial cells. In their latest publication, they examine the expression of VEGF receptors and neuropilins (VEGF coreceptors) in human bladder urothelium in both control and BPS patients.

The authors have found that intravesical instillation of an internalizable VEGF fluorescent tracer into mouse urinary bladders results in a marked ligand accumulation in the urothelium and bladder parenchyma indicating that urothelial VEGF-Rs are functionally active, and capable of ligand interaction and internalization. VEGF receptors and coreceptors (neuropilins) are strongly expressed in the human bladder urothelium. Expression of neuropilin 2 and VEGF-R1 are significantly down-regulated in BPS/IC when compared to control subjects.

Given that neuropilins are expressed outside of the vascular system and play a fundamental role in the activation of inflammatory cells, antigen presenting cells, and effector cells, it is possible that VEGF and neuropilins may have a role in BPS/IC and that their down-regulation could suggest a noninflammatory etiology that would coincide with normal histopathologic findings in a significant proportion of patients. The authors note that glycosaminoglycan modification of neuropilins plays a critical role in modulating VEGF/neuropilin signaling. Previous studies have shown a deficit of chondroitin sulfate on the bladder luminal surface in BPS, suggesting a possible connection between the glycosaminoglycan deficiency and the functionality of this signaling system.

The group conclude that their findings of widespread expression of both neuropilin 1 and 2 in the control and IC urothelia are the first indications that these ubiquitous receptors might play a prominent role - both in control and diseased urinary bladder. Modulating these receptors may eventually be exploited as a therapeutic strategy.

Saban R, Saban MR, Maier J, Fowler B, Tengowski M, Davis CA, Wu XR, Culkin DJ, Hauser P, Backer J, Hurst RE
Am J Physiol Renal Physiol. 2008 Dec;295(6):F1613-23.
doi:10.1152/ajprenal.90344.2008

Written by UroToday.com Contributing Editor Philip M. Hanno, MD, MPH

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