Elevated urinary levels and urothelial expression of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein in patients with interstitial cystitis.
OBJECTIVE
To investigate the pathophysiology of interstitial cystitis (IC), we examined urinary levels and urothelial expression of human orthologue of pancreatitis-associated protein (PAP) III, namely, hepatocarcinoma-intestine-pancreas (HIP)/PAP, in patients with IC. We have previously shown that PAP III is expressed with increased frequency in the bladder urothelium in a rat cystitis model (Takahara Y, et al. J Urol. 2008;179:1603-1609).


METHODS
HIP/PAP levels in the urine from patients with IC were measured by enzyme-linked immunosorbent assay, and HIP/PAP expression in the bladder tissues was assessed by immunohistochemical study.


RESULTS
The median concentration of urinary HIP/PAP was significantly higher in patients with IC than in controls (13.67 vs 1.86 pg/mL urine, respectively, P <.0001, with Mann-Whitney U test). HIP/PAP immunoreactivity was observed in the urothelium of 88.2% of patients with IC (15/17) and in 5.9% of bladder tissues of controls (1/17). Urinary HIP/PAP levels in patients with IC were positively correlated with urinary frequency and bladder pain (r = 0.429, 0.443) and inversely correlated with mean voided urine volume (r = -0.488).


CONCLUSIONS
Urinary HIP/PAP levels were significantly higher in IC patients and the apparent HIP/PAP expression in the bladder urothelium was more frequently observed among IC patients. The involvement of HIP/PAP in the pathophysiology of IC is suggested.
Makino
Tetsuya
T
Department of Anatomy and Neurobiology, Osaka City University Graduate School of Medicine, Osaka, Japan; Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Kawashima
Hidenori
H
Konishi
Hiroyuki
H
Nakatani
Tatsuya
T
Kiyama
Hiroshi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000652:urine*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000652:urine*; D018856:Cystitis, Interstitial / Q000378:metabolism* / Q000652:urine*; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D000073718:Pancreatitis-Associated Proteins; D001743:Urinary Bladder / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat