Extracorporeal Shock Wave Therapy Alters the Expression of Fibrosis-Related Molecules in Fibroblast Derived from Human Hypertrophic Scar

Abstract

Extracorporeal shock wave therapy (ESWT) considerably improves the appearance and symptoms of post-burn hypertrophic scars (HTS). However, the mechanism underlying the observed beneficial effects is not well understood. The objective of this study was to elucidate the mechanism underlying changes in cellular and molecular biology that is induced by ESWT of fibroblasts derived from scar tissue (HTSFs). We cultured primary dermal fibroblasts derived from human HTS and exposed these cells to 1000 impulses of 0.03, 0.1, and 0.3 mJ/mm2. At 24 h and 72 h after treatment, real-time PCR and western blotting were used to detect mRNA and protein expression, respectively, and cell viability and mobility were assessed. While HTSF viability was not affected, migration was decreased by ESWT. Transforming growth factor beta 1 (TGF-β1) expression was reduced and alpha smooth muscle actin (α-SMA), collagen-I, fibronectin, and twist-1 were reduced significantly after ESWT. Expression of E-cadherin was increased, while that of N-cadherin was reduced. Expression of inhibitor of DNA binding 1 and 2 was increased. In conclusion, suppressed epithelial-mesenchymal transition might be responsible for the anti-scarring effect of ESWT, and has potential as a therapeutic target in the management of post-burn scars.

Post-Burn Pruritus

“…The authors hypothesized that focused ESWT might work anti-inflammatorily in this regard. Even an interaction with the numerous cytokines as well as with CGRP appears feasible [78,79].…”

Timing of extracorporeal shock wave therapy in rabbits with carpal tunnel syndrome

“…Some studies have suggested that the increased expression of TGF-ß1 leads to a vicious cycle of SSCT fibrosis in the idiopathic CTS (Chikenji et al, 2014;Gingery et al, 2014). Although the therapeutic mechanisms of ESWT remain unclear, a recent study assessed the expression of fibrosisrelated molecules in fibroblasts derived from human postburn hypertrophic scar tissue after ESWT, revealing significantly reduced expression of TGF-ß1 after ESWT (Cui et al, 2018), which might explain the antiscarring effect of ESWT. The other proposed mechanism of ESWT is that the waves in ESWT dilate blood vessels through enzymatic promotion (Gonkova, Ilieva, Ferriero, & Chavdarov, 2013;Manganotti & Amelio, 2005;Park & Kwon, 2011) and nonenzymatic nitric oxide synthesis (Kwon, Park, Lee, & Chung, 2012), thus inducing neovascularization, increasing the blood supply to the tissue, and activating growth factors.…”

Biological approaches for hypertrophic scars

“…Therefore, targeting both fibroblasts and keratinocytes populations were the novel therapies for scarring . It was shown that extracorporeal shock wave therapy was responsible for the anti‐scarring by suppressing EMT in the post‐burn scars . As such, focus on the dysregulation of injury‐triggered EMT is proved to contribute to HSs treatment.…”

“…124 It was shown that extracorporeal shock wave therapy was responsible for the anti-scarring by suppressing EMT in the post-burn scars. 125 As such, focus on the dysregulation of injury-triggered EMT is proved to contribute to HSs treatment. Keratin and vimentin are characteristic markers of epithelial cells and mesenchymal cells, respectively, and can serve as indicative markers of EMT processes.…”