CXCR3 binding chemokine and TNFSF14 over expression in bladder urothelium of patients with ulcerative interstitial cystitis.
OBJECTIVE
We investigated the genes responsible for ulcerative interstitial cystitis by DNA microarray analysis and quantitative real-time polymerase chain reaction.


METHODS
Bladder urothelial tissues were taken from a site apart from the ulcerative lesion in 9 patients with ulcerative interstitial cystitis and from a normal-looking area in 9 controls, including 7 with bladder carcinoma and 2 with benign prostatic hyperplasia. Total RNA was extracted from bladder samples and gene expression was compared between these 2 groups using Whole Human Genome DNA microarray 44K (Agilent Technologies, Santa Clara, California). Microarray data were analyzed by GeneSpring GX software and Ingenuity Pathway Analysis. Chosen genes were confirmed for altered transcription by quantitative real-time polymerase chain reaction.


RESULTS
We identified 564 probes that were significantly expressed in mRNA more than 4-fold vs those in controls using volcano plot analysis (p <0.001). Further network Ingenuity Pathway Analysis of these genes showed the top 3 functions, including 1) cell-to-cell signaling and interaction, and hematological system development and function, 2) inflammatory disease and 3) cellular development. Quantitative real-time polymerase chain reaction confirmed increased mRNA expression of several genes in the bladder samples of patients with ulcerative interstitial cystitis, including CXCR3 binding chemokines (CXCL9, 10 and 11) and TNFSF14 (LIGHT).


CONCLUSIONS
Our study using DNA microarray analysis followed by quantitative real-time polymerase chain reaction reveals over expression of genes related to immune and inflammatory responses, including T-helper type 1 related chemokines, and cytokines such as CXCR3 binding chemokines and TNFSF14. These genes may be potential interstitial cystitis biomarkers.
Ogawa
Teruyuki
T
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
Homma
Toshiki
T
Igawa
Yasuhiko
Y
Seki
Satoshi
S
Ishizuka
Osamu
O
Imamura
Tetsuya
T
Akahane
Satoshi
S
Homma
Yukio
Y
Nishizawa
Osamu
O
D000368:Aged; D018856:Cystitis, Interstitial / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D054367:Receptors, CXCR3 / Q000096:biosynthesis* / Q000235:genetics*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000096:biosynthesis* / Q000235:genetics*; D014456:Ulcer / Q000235:genetics* / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*; D001745:Urinary Bladder Diseases / Q000235:genetics / Q000378:metabolism; D019459:Urothelium / Q000378:metabolism
C515187:CXCR3 protein, human; D054367:Receptors, CXCR3; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14