Using gene chips to identify organ-specific, smooth muscle responses to experimental diabetes: Potential applications to urological diseases

Jason D. Hipp, Kelvin P. Davies, Moses Tar, Mira Valcic, Abraham Knoll, Arnold Melman, George J. Christ

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

OBJECTIVE: To identify early diabetes-related alterations in gene expression in bladder and erectile tissue that would provide novel diagnostic and therapeutic treatment targets to prevent, delay or ameliorate the ensuing bladder and erectile dysfunction. MATERIALS AND METHODS: The RG-U34A rat GeneChip® (Affymetrix Inc., Sunnyvale, CA, USA) oligonucleotide microarray (containing ≈8799 genes) was used to evaluate gene expression in corporal and male bladder tissue excised from rats 1 week after confirmation of a diabetic state, but before demonstrable changes in organ function in vivo. A conservative analytical approach was used to detect alterations in gene expression, and gene ontology (GO) classifications were used to identify biological themes/pathways involved in the aetiology of the organ dysfunction. RESULTS: In all, 320 and 313 genes were differentially expressed in bladder and corporal tissue, respectively. GO analysis in bladder tissue showed prominent increases in biological pathways involved in cell proliferation, metabolism, actin cytoskeleton and myosin, as well as decreases in cell motility, and regulation of muscle contraction. GO analysis in corpora showed increases in pathways related to ion channel transport and ion channel activity, while there were decreases in collagen I and actin genes. CONCLUSIONS: The changes in gene expression in these initial experiments are consistent with the pathophysiological characteristics of the bladder and erectile dysfunction seen later in the diabetic disease process. Thus, the observed changes in gene expression might be harbingers or biomarkers of impending organ dysfunction, and could provide useful diagnostic and therapeutic targets for a variety of progressive urological diseases/conditions (i.e. lower urinary tract symptoms related to benign prostatic hyperplasia, erectile dysfunction, etc.).

Original languageEnglish (US)
Pages (from-to)418-430
Number of pages13
JournalBJU International
Volume99
Issue number2
DOIs
Publication statusPublished - Feb 1 2007

    Fingerprint

Keywords

  • Bladder dysfunction
  • Diabetes mellitus
  • Erectile dysfunction
  • Gene chips
  • Genomics
  • Microarray analysis
  • Streptozotocin

ASJC Scopus subject areas

  • Urology

Cite this