Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications for treatment of stress urinary incontinence.

Rhabdosphincter (RS) muscle injury occurs during prostatectomy, and is a leading cause of stress urinary incontinence (SUI). Current SUI treatments engender significant side effects, which negatively impact patient quality of life. Thus an unmet need exists to develop novel RS regeneration methods. We have shown that Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and we have developed novel peptide amphiphile nanofiber hydrogel delivery of SHH protein to the penis to regenerate smooth muscle after prostatectomy induced injury. If similar SHH signaling mechanisms regulate RS muscle homeostasis, this innovative technology may be adapted for RS regeneration post-prostatectomy. We examine the SHH pathway in human RS muscle.

Human RS obtained during radical cystoprostatectomy (n = 13), underwent SHH pathway analysis. Primary cultures were established (n = 5), and RS cells were treated with SHH protein, SHH inhibitor, or PBS (control). Immunohistochemical analysis for SHH pathway, skeletal muscle actin, and trichrome stain were performed. RS growth was quantified at 3 and 6 days.

SHH, it is receptors patched and smoothened, and transcriptional activators, GLI proteins, were identified in human RS muscle. At 3 and 6 days, RS cells increased 62% and 78% (P = 0.0001) with SHH treatment and decreased 40% (P = 0.0001) and 18% (P = 0.039) with SHH inhibition.

The SHH pathway was identified in human RS. RS growth increased with SHH treatment, indicating intervention may be possible to enhance RS regeneration, and impact SUI. Peptide amphiphile delivery of SHH may be applicable for RS regeneration and SUI prevention.

Neurourology and urodynamics. 2018 Sep 06 [Epub]

Marah Hehemann, Elizabeth Kalmanek, Shawn Choe, Danuta Dynda, Wen-Yang Hu, Marcus L Quek, Daniel A Harrington, Samuel I Stupp, Kevin T McVary, Carol A Podlasek

Department of Urology, University of Illinois at Chicago, Chicago, Illinois., Division of Urology, Southern Illinois University School of Medicine, Springfield, Illinois., Department of Urology, Loyola University Stritch School of Medicine, Maywood, Illinois., UTHealth, The University of Texas Health Science Center at Houston, Department of Diagnostic and Biomedical Sciences, Houston, Texas., Simpson-Querrey Institute for BioNanotechnology, Department of Chemistry, Department of Materials Science and Engineering, and Biomedical Engineering, Northwestern University, Feinberg School of Medicine, Chicago, Illinois., Departments of Urology, Physiology and Bioengineering, University of Illinois at Chicago, Chicago, Illinois.