Key points are not available for this paper at this time.
You have accessJournal of UrologySexual Function/Dysfunction: Basic Research collagen increases with SHH inhibition and decreases with SHH treatment. We examined if part of the mechanism of how SHH prevents penile remodeling and increased collagen with CN injury, involves bone morphogenetic protein four (BMP4) and GREMLIN (GREM1). The relationship between SHH, BMP4, GREM1 and collagen was examined in the penis of ED patients and rat models of CN injury, SHH inhibition, and SHH, BMP4 and GREM1 treatment. METHODS: Corpora cavernosa of Peyronie's (control), prostatectomy and diabetic ED patients was obtained (n=30). Adult Sprague Dawley rats (n=90) underwent either: 1. CN crush (1-7 days) or sham surgery, 2. CN injury and BMP4, GREM1 or MSA (control) protein treatment via Affi-Gel beads or peptide amphiphile (PA) for 14 days, 3. 5E1 SHH inhibitor, IgG or PBS (control) treatment for 2-4 days. Immunohistochemical and western analysis for BMP-4 and GREM1, and collagen analysis by hydroxyproline and trichrome stain were performed. RESULTS: BMP4 and GREM1 proteins were identified in corpora cavernosa smooth muscle of prostatectomy, diabetic and Peyronie's patients, and in rat smooth muscle, sympathetic nerve fibers, perineurium, blood vessels, and urethra. Hydroxyproline assay showed 25.4% decreased collagen in rats with CN injury and BMP4 treatment (p=0.02) and 61.3% increased collagen with CN injury and GREM1 treatment (p=0.005). Trichrome stain showed increased collagen in rats treated with GREM1. Western analysis identified increased BMP4 and GREM1 in corpora cavernosa of prostatectomy and diabetic patients, and after CN injury (1-2 days) in our rat model. Localization of BMP4 and GREM1 changed with SHH inhibition. SHH treatment increased the monomer form of BMP4 and GREM1, altering their range of signaling. CONCLUSIONS: BMP4 and GREM1 are downstream targets of SHH that impact collagen and may be useful in collaboration with SHH to prevent penile remodeling and ED. A better understanding of penile remodeling and how fibrosis occurs with loss of innervation is essential for development of novel ED therapies. Source of Funding: NIH/NIDDK DK101536 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1086 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Jiangping Deng 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 ...
Deng et al. (Mon,) studied this question.