MP84-06 SONIC HEDGEHOG SIGNALING IN CORPORA CAVERNOSAL CELLS FROM DIABETIC, PROSTATECTOMY, HYPERTENSION AND PEYRONIES PATIENTS WITH ED. (2020)

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP84)1 Apr 2020MP84-06 SONIC HEDGEHOG SIGNALING IN CORPORA CAVERNOSAL CELLS FROM DIABETIC, PROSTATECTOMY, HYPERTENSION AND PEYRONIES PATIENTS WITH ED. Elizabeth Kalmanek, Samuel Ohlander, Daniel Harrington, Samuel Stupp, Kevin McVary, and Carol Podlasek* Elizabeth KalmanekElizabeth Kalmanek More articles by this author , Samuel OhlanderSamuel Ohlander More articles by this author , Daniel HarringtonDaniel Harrington More articles by this author , Samuel StuppSamuel Stupp More articles by this author , Kevin McVaryKevin McVary More articles by this author , and Carol Podlasek*Carol Podlasek* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000976.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Erectile dysfunction (ED) treatments are minimally effective in prostatectomy and diabetic patients due to injury to the cavernous nerve. With denervation the critical smooth muscle undergoes apoptosis and the penis becomes fibrotic, thus altering the corpora cavernosal architecture. In order to devise novel ED therapies, prevention of corpora cavernosal remodeling is critical. In this study we examine the response of human corpora cavernosal cells from several ED patient populations, to determine if ED deriving from other underlying mechanisms than prostatectomy, are responsive to SHH treatment, and we examine other potential signaling molecules critical for smooth muscle growth and regeneration. METHODS: Human corpora cavernosal tissue was obtained from prostatectomy, diabetic, hypertension, and Peyronie’s (control) patients that were under going prosthesis implant to treat ED (n=10). Primary cultures were established, and corpora cavernosal cells were treated with SHH protein, MSA (control), SHH inhibitor, PBS (control), BMP4, and Gremlin (n=6 per group). Growth was quantified at 3-4 days. RESULTS: SHH treatment increased smooth muscle growth in human corpora cavernosal cells from prostatectomy, diabetic, hypertension and Peyronie’s patients in a similar manner (33-51%). There was no difference in growth using 25ug and 10ug SHH peptide. A more active (250X) SHH peptide further enhanced growth, with more pronounced enhancement in corpora cavernosal cells from hypertension patients. BMP4 increased and Gremlin decreased growth in corpora cavernosal cells from hypertension patients, but not in cells from diabetics, or post prostatectomy. CONCLUSIONS: Corpora cavernosa cells from prostatectomy, diabetic, and hypertension patients increased in response to SHH treatment in a similar manner, suggesting that SHH treatment would be beneficial to enhance smooth muscle regeneration in patients with ED of multiple origins. There is a threshold concentration of SHH protein above which smooth muscle growth is enhanced. Tissue from patients with hypertension respond more strongly to lipid modified SHH, and upregulate BMP4 and down regulate Gremlin, suggesting stimulation of fibrotic signaling, that was not present in cells of other ED origin. Understanding how human corpora cavernosal tissue responds to SHH treatment is critical for clinical translation to ED patients. Source of Funding: NIH DK101536 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1266-e1267 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth Kalmanek More articles by this author Samuel Ohlander More articles by this author Daniel Harrington More articles by this author Samuel Stupp More articles by this author Kevin McVary More articles by this author Carol Podlasek* More articles by this author Expand All Advertisement PDF downloadLoading ...