Penile erection induces angiogenic, survival, and antifibrotic signals: molecular events associated with penile erection induced by cavernous nerve stimulation in mice

Abstract

Objectives: To determine the molecular events related to penile erection in the corpus cavernosum tissue of mice after electrical stimulation of the cavernous nerve. Methods: Twelve-week-old male C57BL/6 mice were used in this study. Electrical stimulation of the cavernous nerve was carried out to induce penile erection. Corpus cavernosum tissues were then harvested to determine the effect of nerve-induced penile erection on signaling pathway involved in angiogenesis (vascular endothelial growth factor, hepatocyte growth factor, angiopoietin-1, matrix metalloproteinase 2, and matrix metalloproteinase 9), cell survival and proliferation (phosphatidylinositol 3-kinase, phospho-Akt/Akt, and phospho-ERK/ERK), and tissue fibrosis (phospho-Smad2/Smad2, phospho-Smad3/Smad3, and plasminogen activator inhibitor-1). Results: Cavernous nerve stimulation enhanced the expression of factors involved in angiogenesis (vascular endothelial growth factor, hepatocyte growth factor, angiopoietin-1, matrix metalloproteinase 2, and metalloproteinase 9), and activated intracellular signaling mediators related to cell survival and proliferation (phosphatidylinositol 3-kinase, phospho-Akt/Akt, and phospho-ERK/ERK), while suppressing the pathways involved in tissue fibrosis (phospho-Smad2/Smad2, phospho-Smad3/Smad3, and plasminogen activator inhibitor-1). Conclusions: Penile erection in mice is accompanied by the activation of a cascade of signaling pathways involved in angiogenesis, cell survival and proliferation, and antifibrosis. The present results might provide a theoretical and molecular basis for understanding the importance of penile rehabilitation and subsequent restoration of nocturnal or sexually-mediated penile erections.

Decoding Multiple Biofunctions of Maca on Its Anti-allergic, Anti-inflammatory, Anti-thrombotic, and Pro-angiogenic Activities

“…Moreover, the expression of angiogenic factors, including VEGF, at corpus cavernosum tissue have a critical role in nerve-induced penile erection. VEGF is a potent angiogenic factor which has been shown to recover erectile function on subjects with vasculogenic erectile dysfunction through enhancement of endothelial cell survival and growth . According to this study, the macamide-rich fraction of maca also exhibited a pro-angiogenic effect as VEGF.…”

“…VEGF is a potent angiogenic factor which has been shown to recover erectile function on subjects with vasculogenic erectile dysfunction through enhancement of endothelial cell survival and growth. 31 According to this study, the macamide-rich fraction of maca also exhibited a proangiogenic effect as VEGF. Therefore, it could be a possible candidate in the future of maca study on vascular regeneration and to improve penile erection.…”

A systematic review on cell‐seeded tissue engineering of penile corpora

“…Current developments in biofabrication and microfluidics (Hasan et al, ) might improve vascularization of larger in vitro grown tissue in general and allow more optimal corporal TE. In advanced bioreactors, penile erection could be mimicked in vitro, thereby inducing regeneration with angiogenic and antifibrotic signals like the nocturnal erections are doing for the native corporal tissue (Kwon et al, ). Vascularization will be promoted, as this is a major hurdle in the engineering of tissues and/or organs to clinical relevant sizes (Novosel, Kleinhans, & Kluger, ), and lack of vascularization leads to fibrosis and graft rejection.…”

Molecular Action of Herbal Medicine in Physiology of Erection and its Dysfunction

“…Kwon et al conducted research using the cavernous nerve's electrical stimulation to induce penile erection. Stimulation of the cavernous nerve can increase the expression of factors involved in angiogenesis, cell survival signaling pathways, and intracellular proliferation but decreases signaling activity in tissue fibrosis [74].…”