4.6 Article

Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction

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ELSEVIER
DOI: 10.1016/j.nano.2021.102444

关键词

Peptide amphiphile; Erectile dysfunction; Intrinsic and extrinsic apoptosis; Cavernous nerve injury; Sonic hedgehog; Penis; Peripheral nerve regeneration

资金

  1. NIH/NIDDK [DK101536]

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The research shows that SHH PA can suppress the apoptotic mechanisms of caspase 9 and 8, and inhibiting one mechanism does not shift signaling to the other mechanism.
Erectile dysfunction (ED) is a common and debilitating condition with high impact on quality of life. An underlying cause of ED is apoptosis of penile smooth muscle, which occurs with cavernous nerve injury, in prostatectomy, diabetic and aging patients. We are developing peptide amphiphile (PA) nanofiber hydrogels as an in vivo delivery vehicle for Sonic hedgehog protein to the penis and cavernous nerve to prevent the apoptotic response. We examine two important aspects required for clinical application of the biomaterials: if SHH PA suppresses intrinsic (caspase 9) and extrinsic (caspase 8) apoptotic mechanisms, and if suppressing one apoptotic mechanism forces apoptosis to occur via a different mechanism. We show that SHH PA suppresses both caspase 9 and 8 apoptotic mechanisms, and suppressing caspase 9 did not shift signaling to caspase 8. SHH PA has significant clinical potential as a preventative ED therapy, by management of intrinsic and extrinsic apoptotic mechanisms. Published by Elsevier Inc.

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