Peptide amphiphile nanofiber hydrogel delivery of sonic hedgehog protein to the cavernous nerve to promote regeneration and prevent erectile dysfunction.
Erectile dysfunction (ED) has high impact on quality of life in prostatectomy, diabetic and aging patients. An underlying mechanism is cavernous nerve (CN) injury, which causes ED in up to 80% of prostatectomy patients. We examine how sonic hedgehog (SHH) treatment with innovative peptide amphiphile nanofiber hydrogels (PA), promotes CN regeneration after injury. SHH and its receptors patched (PTCH1) and smoothened (SMO) are localized in PG neurons and glia. SMO undergoes anterograde transport to signal to downstream targets. With crush injury, PG neurons degenerate and undergo apoptosis. SHH protein decreases, SMO localization changes to the neuronal cell surface, and anterograde transport stops. With SHH treatment SHH is taken up at the injury site and undergoes retrograde transport to PG neurons, allowing SMO transport to occur, and neurons remain intact. SHH treatment prevents neuronal degeneration, maintains neuronal, glial and downstream target signaling, and is significant as a regenerative therapy.
Department of Urology, University of Illinois at Chicago, Chicago, IL, USA.
Shawn
S
Choe
Department of Allergy/Immunology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Christopher W
CW
Bond
Department of Biosciences, Rice University, Houston, TX, USA.
Daniel A
DA
Harrington
Simpson-Querrey Institute for BioNanotechnology, Department of Chemistry, Department of Materials Science and Engineering, and Biomedical Engineering, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Samuel I
SI
Stupp
Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Kevin T
KT
McVary
Departments of Urology, Physiology and Bioengineering, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: cap325@uic.edu.
Carol A
CA
Podlasek
D000818:Animals; D007172:Erectile Dysfunction / Q000188:drug therapy*; D053823:Hedgehog Proteins / Q000008:administration & dosage*; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D057139:Nanofibers / Q000737:chemistry*; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects*; D010413:Penis / Q000294:innervation*; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000072086:Smoothened Receptor / Q000378:metabolism
D053823:Hedgehog Proteins; D020100:Hydrogels; D010455:Peptides; C498555:Smo protein, rat; D000072086:Smoothened Receptor
Cavernous nerve injury (prostatectomy); Erectile dysfunction; Peptide amphiphile nanofiber hydrogel; Regeneration; Sonic hedgehog