Peptide amphiphile delivery of sonic hedgehog protein promotes neurite formation in penile projecting neurons.
Erectile dysfunction (ED) critically impacts quality of life in prostatectomy, diabetic and aging patients. The underlying mechanism involves cavernous nerve (CN) damage, resulting in ED in 80% of prostatectomy patients. Peptide amphiphile (PA) nanofiber hydrogel delivery of sonic hedgehog (SHH) protein to the injured CN, improves erectile function by 60% at 6 weeks after injury, by an unknown mechanism. We hypothesize that SHH is a regulator of neurite formation. SHH treatment promoted extensive neurite formation in uninjured and crushed CNs, and SHH inhibition decreased neurites >80%. Most abundant neurites were observed with continuous SHH PA treatment of crushed CNs. Once induced with SHH, neurites continued to grow. SHH rescued neurite formation when not given immediately. SHH is a critical regulator of neurite formation in peripheral neurons under uninjured and regenerative conditions, and SHH PA treatment at the time of injury/prostatectomy provides an exploitable avenue for intervention to prevent ED.
['Dobbs|Ryan|R|', 'Choe|Shawn|S|', 'Kalmanek|Elizabeth|E|', 'Harrington|Daniel A|DA|', 'Stupp|Samuel I|SI|', 'McVary|Kevin T|KT|', 'Podlasek|Carol A|CA|']
D000818:Animals D016503:Drug Delivery Systems D053823:Hedgehog Proteins D020100:Hydrogels D008297:Male D057139:Nanofibers D016501:Neurites D055495:Neurogenesis D010413:Penis D010446:Peptide Fragments D051381:Rats D017207:Rats, Sprague-Dawley
Sonic hedgehog Neurite formation Cavernous nerve injury Pelvic ganglia Peptide amphiphile nanofiber hydrogel Peripheral nerve regeneration Schwann cells