Cellular signaling pathways modulated by low-intensity extracorporeal shock wave therapy

Abstract

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is a form of energy transfer that is of lower intensity (<0.2mJ/mm2) relative to traditional Extracorporeal Shock Wave Lithotripsy (ESWL) used for management of urinary stones. At this intensity and at appropriate dosing energy transfer is thought to induce beneficial effects in human tissues. The proposed therapeutic mechanisms of action for Li-ESWT include neovascularization, tissue regeneration, and reduction of inflammation. These effects are thought to be mediated by enhanced expression of vascular endothelial growth factor, endothelial nitric oxide synthase, and proliferating cell nuclear antigen. Upregulation of chemoattractant factors and recruitment/activation of stem/progenitor cells may also play a role. Li-ESWT has been studied for management of musculoskeletal disease, ischemic cardiovascular disorders, Peyronie's Disease, and more recently erectile dysfunction (ED). The underlying mechanism of Li-ESWT for treatment of ED is incompletely understood. We summarize the current evidence basis by which Li-ESWT is thought to enhance penile hemodynamics with an intention of outlining the fundamental mechanisms by which this therapy may help manage ED.

Figures

Fig 1. Cellular signaling pathways modulated by Low-intensity Extracorporeal Shock Wave Therapy (Li-ESWT)

Li-ESWT: Low-intensity extracorporeal shock wave therapy; Frizzled: receptor of WNT; BDNF: Brain-derived neurotrophic factor; GSK-3β: Glycogen synthase kinase-3 beta; β-Cat: beta-catenin; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B (PKB), also known as Akt; Src: Src is short for sarcoma, a Proto-oncogene tyrosine-protein kinase Src; TSC2: Tuberous Sclerosis Complex 2; GFR: growth factor receptor; RAS: molecules of MAPK/ERK pathway; RAF: molecules of MAPK/ERK pathway; MEK: mitogen-activated protein kinase kinase; mTORC1:mammalian target of rapamycin complex 1; FAK: Focal Adhesion Kinase; VEGF: Vascular Endothelial Growth Factor ; SOS: Son of Sevenless

Fig 2. Low-intensity Extracorporeal Shock Wave Therapy Modulated Unfolded Protein Response (UPR)

IRE1a: inositol-requiring enzyme 1α; S1P: Sphingosine-1-phosphate; S2P: Sphingosine-2-phosphate; ATF: activated transcription factor; BiP: Immunoglobulin heavy-chain-binding protein; XBP1u: un-spliced X-box binding protein 1; XBP1s: spliced X-box binding protein 1; PERK: Protein kinase R-like endoplasmic reticulum kinase; eIF2: eukaryotic initiation factor 2