UroToday – Urothelial Expression of Hepatocarcinoma-Intestine-pancreas/Pancreatitis-associated Protein (HIP)/(PAP) Expressed in Patients with Interstitial Cystitis.

A protein called regenerating gene was originally identified in regenerating pancreatic islet cells. A family of related genes has been identified and described under a rather varied nomenclature such as PAP and HIP and has been broadly categorized into 4 subtypes. Recently, it was assumed that HIP/PAP expression is associated with inflammation because it is expressed as a secretory protein in acute pancreatitis, and is expressed in human gut epithelial cells in inflammatory bowel disease.

Dr. Tetsuya Makino and colleagues from Osaka, Japan have demonstrated in a rat cyclophosamide cystitis model that PAP III is expressed in the urothelium of the bladder and PAP I was expressed in the primary afferent neurons of dorsal root ganglia that innervate the bladder. Now, the same group has looked at urothelium in BPS/IC patients. Twenty-seven females who met NIDDK criteria for IC were compared with 27 female controls. Positive staining of the urothelium for HIP/PAP was found in 15/17 IC patients and 1/17 controls. Urinary levels of HIP/PAP in IC patients were higher than those in normal controls. Increased immunoreactivity for HIP/PAP was frequently observed in the umbrella cells of the urothelium in IC patients, suggesting that expression of HIP/PAP is induced in the urothelium and then released into the urine of IC patients. Urinary levels correlated with severity of urinary symptoms.

The researchers conclude that the intense HIP/PAP immunoreactivity in the umbrella cell layer in IC patients suggests that umbrella cells have a crucial role as an anti-inflammatory mediator. HIP/PAP could be another candidate for a BPS/IC marker, and may help to reveal the ultimate pathophysiology of this syndrome.

Makino T, Kawashima H, Konishi H, Nakatani T, Kiyama H
Urology. 2009 Jul 29. Epub ahead of print.
doi:10.1016/j.urology.2009.05.044

UroToday Contributing Editor Philip M. Hanno, MD, MPH

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