Differentiation Associated Changes in Gene Expression Profiles of Interstitial Cystitis and Control Urothelial Cells

Deborah R. Erickson, Steven R. Schwarze, Justin K. Dixon, Curtis J. Clark, Matt A. Hersh

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Purpose: We evaluated gene expression profiles after inducing differentiation in cultured interstitial cystitis and control urothelial cells. Materials and Methods: Bladder biopsies were taken from patients with interstitial cystitis and controls, that is women undergoing surgery for stress incontinence. Primary cultures were grown in keratinocyte growth medium with supplements. To induce differentiation in some plates the medium was changed to Dulbecco's modified Eagle's minimal essential medium-F12 (Media Tech, Herndon, Virginia) with supplements. RNA was analyzed with Affymetrix® chips. Three patients with nonulcerative interstitial cystitis were compared with 3 controls. Results: After inducing differentiation 302 genes with a described function were altered at least 3-fold in interstitial cystitis and control cells (p <0.01). Functions of the 162 up-regulated genes included cell adhesion (eg claudins, occludin and cingulin), urothelial differentiation, the retinoic acid pathway and keratinocyte differentiation (eg skin cornified envelope components). The 140 down-regulated transcripts included genes associated with basal urothelium (eg p63, integrins β4, α5 and α6, basonuclin 1 and extracellular matrix components), vimentin, metallothioneins, and members of the Wnt and Notch pathways. When comparing interstitial cystitis control cells after differentiation, only 7 genes with a described function were altered at least 3-fold (p <0.01). PI3, SERPINB4, CYP2C8, EFEMP2 and SEPP1 were decreased, and AKR1C2 and MKNK1 were increased in interstitial cystitis cases. Conclusions: Differentiation associated changes occurred in interstitial cystitis and control cells. Comparing interstitial cystitis vs control cases revealed few differences. This study may have included patients with interstitial cystitis and minimal urothelial deficiency, and/or we may have selected cells that were most robust in culture. Also, the abnormal urothelium in interstitial cystitis cases may be due to post-translational changes and/or to the bladder environment.

Original languageEnglish
Pages (from-to)2681-2687
Number of pages7
JournalJournal of Urology
Volume180
Issue number6
DOIs
StatePublished - Dec 2008

Bibliographical note

Funding Information:
Supported by a University of Kentucky Microarray Pilot Grant, Division of Urology and Endowment for Neuro-urological Research.

Keywords

  • cystitis, interstitial
  • gene expression
  • microarray analysis
  • urinary bladder
  • urothelium

ASJC Scopus subject areas

  • Urology

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