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

Hui Cui,Cheong Seo,A Ram Hong,Yoon Cho,Joo Yu,So Joo,June-Bum Kim

doi:10.3390/ijms19010124

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.

Highlights

Post-burn hypertrophic scars (HTSs) are a most common complication of burn injury and result from excessive scar tissue formation in prolonged aberrant wound healing, and are characterized by hyalinized collagen bundles
To determine the character of HTSFs, we conducted western blot analysis. epithelial-mesenchymal transition (EMT) markers were significantly more strongly expressed by HTSFs than by human normal fibroblasts (HNFs) of the same passage
Protein expression of TGF-β1, α-SMA, collagen-I, collagen-III, fibronectin, vimentin, fibroblast specific protein 1 (FSP-1), E-cadherin, and twist1 was significantly higher in HTSFs than in HNFs (Figure 1)

Summary

Introduction

Post-burn hypertrophic scars (HTSs) are a most common complication of burn injury and result from excessive scar tissue formation in prolonged aberrant wound healing, and are characterized by hyalinized collagen bundles. They can functionally (arthrentasis), symptomatically (pruritis, pain), and aesthetically impact the patient’s quality of life. The pathophysiology of HTS formation involves an overactive proliferative phase in wound healing [2]. Activated T cells, macrophages, and Langerhans cells disrupt normal wound healing and tissue remodeling, and contribute to abnormal extracellular matrix (ECM) accumulation with an increased cellular activity [3,4]

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