The Role of Hedgehog-interacting Protein in Maintaining Cavernous Nerve Integrity and Adult Penile Morphology

Overview

Journal J Sex Med

Publisher Oxford University Press

Specialties Gynecology & Obstetrics
Reproductive Medicine
Urology

Date 2009 Jun 12

PMID 19515211

Citations 7

Authors

Nicholas L Angeloni

Christopher W Bond

Diana Monsivais

Yi Tang

Carol A Podlasek

Affiliations

Soon will be listed here.

Abstract

Introduction: Sonic hedgehog (SHH) is an essential regulator of smooth muscle apoptosis in the penis that has significant clinical potential as a therapy to suppress post-prostatectomy apoptosis, an underlying cause of erectile dysfunction (ED). Thus an understanding of how SHH signaling is regulated in the adult penis is essential to move the field of ED research forward and to develop new treatment strategies. We propose that hedgehog-interacting protein (HIP), which has been shown to bind SHH protein and to play a role in SHH regulation during embryogenesis of other organs, is a critical regulator of SHH signaling, penile morphology, and apoptosis induction.

Aims: We have examined HIP signaling in the penis and cavernous nerve (CN) during postnatal differentiation of the penis, in CN-injured, and a diabetic model of ED.

Methods: HIP localization/abundance and RNA abundance were examined by immunohistochemical (IHC) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in Sprague-Dawley rats between the ages of 7 and 92 days old, in CN-injured Sprague-Dawley rats and in BioBreeding/Worcester diabetic rats. HIP signaling was perturbed in the pelvic ganglia and in the penis and TUNEL assay was performed in the penis. CN tie, lidocaine, and anti-kinesin experiments were performed to examine HIP signaling in the CN and penis.

Results: In this study we are the first to demonstrate that HIP undergoes anterograde transport to the penis via the CN, that HIP perturbation in the pelvic ganglia or the penis induces apoptosis, and that HIP plays a role in maintaining CN integrity, penile morphology, and SHH abundance.

Conclusions: These studies are significant because they show HIP involvement in cross-talk (signaling) between the pelvic ganglia and penis, which is integral for maintenance of penile morphology and they suggest a mechanism of how nerves may regulate target organ morphology and function.

Citing Articles

Molecular pathogenesis and treatment of cavernous nerve injury-induced erectile dysfunction: A narrative review.

Song G, Hu P, Song J, Liu J, Ruan Y Front Physiol. 2022; 13:1029650.

PMID: 36277218 PMC: 9582663. DOI: 10.3389/fphys.2022.1029650.

Peptide amphiphile nanofiber hydrogel delivery of sonic hedgehog protein to the cavernous nerve to promote regeneration and prevent erectile dysfunction.

Choe S, Bond C, Harrington D, Stupp S, McVary K, Podlasek C Nanomedicine. 2016; 13(1):95-101.

PMID: 27609775 PMC: 5333775. DOI: 10.1016/j.nano.2016.08.032.

Nitric Oxide Synthase is Necessary for Normal Urogenital Development.

Bond C, Cakir O, McVary K, Podlasek C Andrology (Los Angel). 2014; 2:108.

PMID: 24900949 PMC: 4041737. DOI: 10.4172/2167-0250.1000108.

Sonic hedgehog is neuroprotective in the cavernous nerve with crush injury.

Angeloni N, Bond C, Harrington D, Stupp S, Podlasek C J Sex Med. 2012; 10(5):1240-50.

PMID: 22994531 PMC: 3637863. DOI: 10.1111/j.1743-6109.2012.02930.x.

Spontaneous recovery of cavernous nerve crush injury.

Kim H, Kim H, Kim S, Lee S, Lee W, Yang D Korean J Urol. 2011; 52(8):560-5.

PMID: 21927704 PMC: 3162223. DOI: 10.4111/kju.2011.52.8.560.

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