title: Increased mRNA expression of genes involved in pronociceptive inflammatory reactions in bladder tissue of interstitial cystitis.
abstract: OBJECTIVE
  We assayed mRNA expression of the TRP family of channels and ASIC1 in bladder tissue from patients with interstitial cystitis.
  
  
  METHODS
  Bladder biopsies of 1) nonclassic interstitial cystitis, 2) nonulcerative portions of classic interstitial cystitis, 3) ulcerative portions of classic interstitial cystitis and 4) noncancerous portions of bladder cancer as the control were placed immediately in ice-cold RNAlater® and subjected to real-time reverse transcriptase-polymerase chain reaction. We compared the mRNA expression of TRP channels, ASIC1, NGF, CXCL9 and UPK3A with that of controls, and correlated expression with symptom severity.
  
  
  RESULTS
  We analyzed specimens from 17 patients with nonclassic interstitial cystitis, 22 with classic interstitial cystitis and 11 controls. In nonclassic interstitial cystitis samples TRPV2 and NGF showed significantly increased expression. In classic interstitial cystitis samples nonulcerative portions demonstrated a significant increase in the expression of TRPA1, TRPM2 and 8, TRPV1 and 2, ASIC1, NGF and CXCL9, and a significant decrease in UPK3A and TRPV4. Ulcerative portions showed similar changes for TRPM2, TRPV1, 2 and 4, CXCL9 and UPK3A. Increased expression of TRPM2, first noted in interstitial cystitis tissue, was the most pronounced one of the TRP family. All symptom measures correlated with TRPM2 and TRPV2 expression, and partially with that of the other genes.
  
  
  CONCLUSIONS
  This study showed increased expression of the genes involved in pronociceptive inflammatory reactions in interstitial cystitis, including TRPV1, 2 and 4, ASIC1, NGF and CXCL9, and to our knowledge TRPM2 for the first time. The different expression patterns suggest distinct pathophysiologies for classic and nonclassic interstitial cystitis. The genes and their products are potential candidates for use as biomarkers or novel therapy targets.
authors.affiliation: Department of Urology, University of Tokyo, Tokyo, Japan. Electronic address: homma-uro@umin.ac.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.forename: Akira
authors.initials: A
authors.lastname: Nomiya
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tagaya
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oyama
authors.forename: Kazuchika
authors.initials: K
authors.lastname: Takagaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018856:Cystitis, Interstitial / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D040542:Mechanotransduction, Cellular; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D013697:Thermosensing; D055815:Young Adult
chemical_list: D012333:RNA, Messenger
keywords: ASIC; CXCL9; GAPDH; IC; NGF; OSPI; OSSI; O’Leary-Sant problem score; O’Leary-Sant symptom score; RT; TRP; TRP ankyrin; TRP melastatin; TRP vanilloid; TRPA; TRPM; TRPV; UPK; VAS; acid sensing ion channel; chemokine (C-X-C motif) ligand 9; cystitis; gene expression; glyceraldehyde-3-phosphate dehydrogenase; interstitial; interstitial cystitis; nerve growth factor; qRT-PCR; quantitative real-time RT-polymerase chain reaction; reverse transcriptase; transient receptor potential; transient receptor potential channels; urinary bladder; uroplakin; uroplakins; visual analog pain scale