Mp66-06 SHH Regulates Penile Morphology and Smooth Muscle Through a Mechanism Involving Bmp4 and Grem1

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP66)1 May 2024MP66-06 SHH REGULATES PENILE MORPHOLOGY AND SMOOTH MUSCLE THROUGH A MECHANISM INVOLVING BMP4 AND GREM1 Jiangping Deng, Sarah Martin, Timothy Searl, Samuel Ohlander, Daniel Harrington, Kevin McVary, and Carol A. Podlasek Jiangping DengJiangping Deng , Sarah MartinSarah Martin , Timothy SearlTimothy Searl , Samuel OhlanderSamuel Ohlander , Daniel HarringtonDaniel Harrington , Kevin McVaryKevin McVary , and Carol A. PodlasekCarol A. Podlasek View All Author Informationhttps://doi.org/10.1097/01.JU.0001009468.01097.19.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The cavernous nerve (CN) is frequently damaged in prostatectomy and diabetic patients with ED, initiating changes in penile morphology including an acute and intense phase of apoptosis in penile smooth muscle and increased collagen, which alter penile architecture, make corpora cavernosa smooth muscle less able to relax in response to neurotransmitters, and ED results. Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and SHH treatment suppresses penile remodeling after CN injury through an unknown mechanism; we examine if part of the mechanism of how SHH preserves smooth muscle after CN injury involves bone morphogenetic protein 4 (BMP4) and GREMLIN (GREM1). METHODS: Primary cultures of smooth muscle cells were established from prostatectomy, diabetic, hypertension and Peyronie's (control, n=18) patients. Cultures were characterized by ACTA2, CD31, P4HB and nNOS immunohistochemical analysis. Patient smooth muscle cell growth was quantified in response to BMP4 and GREM1 treatment. Adult Sprague Dawley rats underwent 1 of 3 surgeries: 1) Uninjured or CN injured rats were treated with BMP4, GREM1 or MSA (control) proteins via Affi-Gel beads (n=16) or peptide amphiphile (PA, n=26) for 3 and 14 days, and trichrome stain was performed. 2) Rats underwent sham (n=3), CN injury (n=9), or CN injury and SHH PA treatment for 1, 2 and 4 days (n=9) and western for BMP4 and GREM1 was performed. 3) Rats were treated with 5E1 SHH inhibitor (n=6) or IgG (control, n=6) for 2 and 4 days, and BMP4 and GREM1 localization was examined. Statistics were performed by ANOVA with Scheffe's posthoc test. RESULTS: BMP-4 increased patient smooth muscle cell growth, and GREM1 decreased growth. In uninjured and CN injured rats, BMP4 treatment via Aff-Gel beads and PA increased smooth muscle at 3 and 14 days of treatment. GREM1 treatment caused increased collagen and smooth muscle at 3 days, which switched to primarily collagen at 14 days. CN injury increased BMP4 and GREM1 while SHH PA altered western band size suggesting alternative cleavage and range of BMP4 and GREM1 signaling. SHH inhibition in rats increased BMP4 and GREM1 in fibroblasts. CONCLUSIONS: SHH treatment alters BMP4 and GREM1 localization and range of signaling, which can affect penile morphology. Part of the mechanism of how SHH regulates corpora cavernosa smooth muscle, involves BMP4 and GREM1. Understanding how SHH PA preserves and regenerates penile morphology after CN injury will aid development of ED therapies. Source of Funding: NIH/NIDDK DK101536 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1087 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Jiangping Deng More articles by this author Sarah Martin More articles by this author Timothy Searl More articles by this author Samuel Ohlander More articles by this author Daniel Harrington More articles by this author Kevin McVary More articles by this author Carol A. Podlasek More articles by this author Expand All Advertisement PDF downloadLoading ...