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

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

Research output: Contribution to journalArticle

Abstract

Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)2551-2559
Number of pages9
JournalNeurourology and Urodynamics
Volume37
Issue number8
DOIs
Publication statusPublished - Nov 1 2018

Fingerprint

Stress Urinary Incontinence
Regeneration
Prostatectomy
Hedgehog Proteins
Muscles
Smooth Muscle
Nanofibers
Peptides
Hydrogel
Penis
Wounds and Injuries
Therapeutics
Growth
Actins
Skeletal Muscle
Homeostasis
Quality of Life
Technology
Proteins

Keywords

  • muscle regeneration
  • rhabdosphincter
  • Sonic hedgehog
  • stress urinary incontinence

ASJC Scopus subject areas

  • Clinical Neurology
  • Urology

Cite this

Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications for treatment of stress urinary incontinence. / Hehemann, Marah; Kalmanek, Elizabeth; Choe, Shawn; Dynda, Danuta; Hu, Wen Yang; Quek, Marcus L.; Harrington, Daniel A.; Stupp, Samuel I; McVary, Kevin T.; Podlasek, Carol A.

In: Neurourology and Urodynamics, Vol. 37, No. 8, 01.11.2018, p. 2551-2559.

Research output: Contribution to journalArticle

Hehemann, M, Kalmanek, E, Choe, S, Dynda, D, Hu, WY, Quek, ML, Harrington, DA, Stupp, SI, McVary, KT & Podlasek, CA 2018, 'Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications for treatment of stress urinary incontinence', Neurourology and Urodynamics, vol. 37, no. 8, pp. 2551-2559. https://doi.org/10.1002/nau.23813
Hehemann, Marah ; Kalmanek, Elizabeth ; Choe, Shawn ; Dynda, Danuta ; Hu, Wen Yang ; Quek, Marcus L. ; Harrington, Daniel A. ; Stupp, Samuel I ; McVary, Kevin T. ; Podlasek, Carol A. / Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications for treatment of stress urinary incontinence. In: Neurourology and Urodynamics. 2018 ; Vol. 37, No. 8. pp. 2551-2559.
@article{e50185ab74c44d3bab6496bab7e83ec0,
title = "Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications for treatment of stress urinary incontinence",
abstract = "Aims: 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. Methods: 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. Results: 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. Conclusions: 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.",
keywords = "muscle regeneration, rhabdosphincter, Sonic hedgehog, stress urinary incontinence",
author = "Marah Hehemann and Elizabeth Kalmanek and Shawn Choe and Danuta Dynda and Hu, {Wen Yang} and Quek, {Marcus L.} and Harrington, {Daniel A.} and Stupp, {Samuel I} and McVary, {Kevin T.} and Podlasek, {Carol A.}",
year = "2018",
month = "11",
day = "1",
doi = "10.1002/nau.23813",
language = "English",
volume = "37",
pages = "2551--2559",
journal = "Neurourology and Urodynamics",
issn = "0733-2467",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications for treatment of stress urinary incontinence

AU - Hehemann, Marah

AU - Kalmanek, Elizabeth

AU - Choe, Shawn

AU - Dynda, Danuta

AU - Hu, Wen Yang

AU - Quek, Marcus L.

AU - Harrington, Daniel A.

AU - Stupp, Samuel I

AU - McVary, Kevin T.

AU - Podlasek, Carol A.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - muscle regeneration

KW - rhabdosphincter

KW - Sonic hedgehog

KW - stress urinary incontinence

UR - http://www.scopus.com/inward/record.url?scp=85053235143&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053235143&partnerID=8YFLogxK

U2 - 10.1002/nau.23813

DO - 10.1002/nau.23813

M3 - Article

VL - 37

SP - 2551

EP - 2559

JO - Neurourology and Urodynamics

JF - Neurourology and Urodynamics

SN - 0733-2467

IS - 8

ER -