Regulation of cavernous nerve injury-induced apoptosis by sonic hedgehog.
Thirty to eighty-seven percent of patients treated by radical prostatectomy experience erectile dysfunction (ED). The reduced efficacy of treatments in this population makes novel therapeutic approaches to treat ED essential. We propose that abundant apoptosis observed in penile smooth muscle when the cavernous nerve (CN) is cut (mimicking the neural injury which can result from prostatectomy) is a major contributing factor to ED development. We hypothesize that decreased Sonic hedgehog (SHH) signaling is a cause of ED in neurological models of impotence by increasing apoptosis in penile smooth muscle. We examined this hypothesis in a bilateral CN injury model of ED. We found that the active form of SHH protein was significantly decreased 1.2-fold following CN injury, that SHH inhibition causes a 12-fold increase in smooth muscle apoptosis in the penis, and that SHH treatment at the time of CN injury was able to decrease CN injury-induced apoptosis (1-3-fold) in a dose-dependent manner. These results show that SHH stabilizes the alterations of the corpora cavernosal smooth muscle following nerve injury.
Podlasek
Carol A
CA
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA. cap325@northwestern.edu
Meroz
Cynthia L
CL
Tang
Yi
Y
McKenna
Kevin E
KE
McVary
Kevin T
KT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D007172:Erectile Dysfunction / Q000209:etiology* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D000072079:Patched Receptors; D010413:Penis / Q000737:chemistry / Q000294:innervation / Q000473:pathology*; D059348:Peripheral Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism
D053823:Hedgehog Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface