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


METHODS
The RG-U34A rat GeneChip (Affymetrix Inc., Sunnyvale, CA, USA) oligonucleotide microarray (containing approximately 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.).
Hipp
Jason D
JD
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
Davies
Kelvin P
KP
Department of Urology, Albert Einstein College of Medicine, Bronx, NY, USA.
Tar
Moses
M
Department of Urology, Albert Einstein College of Medicine, Bronx, NY, USA.
Valcic
Mira
M
Department of Urology, Albert Einstein College of Medicine, Bronx, NY, USA.
Knoll
Abraham
A
Department of Urology, Albert Einstein College of Medicine, Bronx, NY, USA.
Melman
Arnold
A
Department of Urology, Albert Einstein College of Medicine, Bronx, NY, USA.
Christ
George J
GJ
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.|Department of Urology and Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D015870:Gene Expression; D023281:Genomics; D008297:Male; D009130:Muscle, Smooth / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D001745:Urinary Bladder Diseases / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology