title: Proteomic investigation on chronic bladder irritation in the rat.
abstract: OBJECTIVE
  Interstitial cystitis (IC) is a painful bladder syndrome associated with urinary frequency and urgency. Elusive cause of IC makes its diagnosis only possible by exclusion in many cases. In this study, we used proteomics for identifying disease-associated proteins in a rat model of chronic bladder irritation.
  
  
  METHODS
  Chronic irritation of the rat bladder was caused by a brief (90 seconds) intravesical instillation of 0.2 mL of 0.4 N HCl. Whole bladders were collected at different time points after treatment, snap frozen, and nuclear and cytosolic protein extracts were obtained. Samples were resolved in standard 2-dimensional (2D) gels stained with an improved Coomasie stain or by differential gel electrophoresis (DIGE). Differentially expressed spots were excised and identified by MALDI-TOF MS/MS. Histologic and Western blot analyses were also performed.
  
  
  RESULTS
  Bladder morphology and histologic appearance of bladder sections after HCl treatment reflected hemorrhage, edema, epithelial denudation, detrusor mastocytosis, and eosinophilia. Proteomic analysis of irritated rat bladder revealed marked overexpression of 4 nuclear proteins and marked underexpression of 1 nuclear protein compared with normal rat bladders. Among these proteins, inflammation-associated calgranulin A (over) and smooth muscle protein-22/transgelin (under) showed opposed expression patterns after bladder irritation.
  
  
  CONCLUSIONS
  Presence of mast cells and eosinophils and overexpression of calgranulin A confirm the inflammatory component of HCl-irritated bladder. Altered expression of nuclear proteins is of particular interest because of their possible role as a prognostic marker in inflammatory bladder disorders. However, more studies are needed before clinical application of these findings can be established.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine; Pittsburgh, Pennsylvania 15213, USA. tyagip@upmc.edu
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.forename: Xuan
authors.initials: X
authors.lastname: Chen
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: Fernando
authors.initials: F
authors.lastname: de Miguel
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003556:Cystitis / Q000473:pathology; D005260:Female; D011506:Proteins / Q000032:analysis*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000737:chemistry*
chemical_list: D011506:Proteins