Lower energy radial shock wave therapy improves characteristics of hypertrophic scar in a rabbit ear model

Zhao,Jing‑Chun; Zhang,Bo‑Ru; Shi,Kai; Wang,Jian; Yu,Qing-Hua; Yu,Jia‑Ao

doi:10.3892/etm.2017.5441

Lower energy radial shock wave therapy improves characteristics of hypertrophic scar in a rabbit ear model

Authors:
- Jing‑Chun Zhao
- Bo‑Ru Zhang
- Kai Shi
- Jian Wang
- Qing-Hua Yu
- Jia‑Ao Yu
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Affiliations: Burns and Plastic Reconstruction Unit, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: November 6, 2017 https://doi.org/10.3892/etm.2017.5441
Pages: 933-939
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the effects of radial extracorporeal shock wave therapy (rESWT) on scar characteristics and transforming growth factor (TGF)‑β1/Smad signaling in order to explore a potential modality for the treatment of hypertrophic scars (HS). The HS model was generated in rabbit ears, then rabbits were randomly divided into 3 groups: Lower (L)‑ESWT [treated with rESWT with lower energy flux density (EFD) of 0.1 mJ/mm2], higher (H)‑ESWT (treated with a higher EFD of 0.18 mJ/mm2) and the sham ESWT group (S‑ESWT; no ESWT treatment). Scar characteristics (wrinkles, texture, diameter, area, volume of elevation, hemoglobin and melanin) were assessed using the Antera 3D® system. The protein and mRNA expression of TGF‑β1, Smad2, Smad3 and Smad7 was assessed by enzyme‑linked immunosorbent assay and reverse transcription‑quantitative polymerase chain reaction, respectively. The Antera 3D® results indicated that wrinkles and hemoglobin of the HS were significantly improved in both of the rESWT groups when compared with the S‑ESWT group. However, these changes appeared much earlier in the L‑ESWT group than the H‑ESWT. Scar texture was also improved in the L‑ESWT group. However, rESWT did not influence HS diameter, area, volume of elevation or melanin levels. rESWT had no effect on TGF‑β1 or Smad7 expression in either of rESWT groups. Although no difference was observed in Smad2 mRNA expression in the L‑ESWT group, the Smad3 mRNA and protein expression significantly decreased when compared with the H‑ESWT and S‑ESWT groups. By contrast, Smad2 and Smad3 mRNA expression were upregulated in the H‑ESWT group. These results demonstrated that rESWT with 0.1 mJ/mm2 EFD improved some characteristics of the HS tissue. Downregulation of Smad3 expression may underlie this inhibitory effect. Inhibition of the TGF‑β1/Smad signal transduction pathway may be a potential therapeutic target for the management of HS.

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1	Gauglitz GG, Korting HC, Pavicic T, Ruzicka T and Jeschke MG: Hypertrophic scarring and keloids: Pathomechanisms and current and emerging treatment strategies. Mol Med. 17:113–125. 2011. View Article : Google Scholar : PubMed/NCBI
2	Niessen FB, Spauwen PH, Schalkwijk J and Kon M: On the nature of hypertrophic scars and keloids: A review. Plast Reconstr Surg. 104:1435–1458. 1999. View Article : Google Scholar : PubMed/NCBI
3	Hardy MA: The biology of scar formation. Phys Ther. 69:1014–1024. 1989. View Article : Google Scholar : PubMed/NCBI
4	Hayashida T, Decaestecker M and Schnaper HW: Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells. FASEB J. 17:1576–1578. 2003.PubMed/NCBI
5	Asano Y, Ihn H, Yamane K, Jinnin M, Mimura Y and Tamaki K: Phosphatidylinositol 3-kinase is involved in alpha2(I) collagen gene expression in normal and scleroderma fibroblasts. J Immunol. 172:7123–7135. 2004. View Article : Google Scholar : PubMed/NCBI
6	Zhu Z, Ding J, Shankowsky HA and Tredget EE: The molecular mechanism of hypertrophic scar. J Cell Commun Signal. 7:239–252. 2013. View Article : Google Scholar : PubMed/NCBI
7	Klass BR, Grobbelaar AO and Rolfe KJ: Transforming growth factor beta1 signalling, wound healing and repair: A multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgrad Med J. 85:9–14. 2009. View Article : Google Scholar : PubMed/NCBI
8	Trisliana Perdanasari A, Torresetti M, Grassetti L, Nicoli F, Zhang YX, Dashti T, Di Benedetto G and Lazzeri D: Intralesional injection treatment of hypertrophic scars and keloids: A systematic review regarding outcomes. Burns Trauma. 3:142015. View Article : Google Scholar : PubMed/NCBI
9	Steinstraesser L, Flak E, Witte B, Ring A, Tilkorn D, Hauser J, Langer S, Steinau HU and Al-Benna S: Pressure garment therapy alone and in combination with silicone for the prevention of hypertrophic scarring: Randomized controlled trial with intraindividual comparison. Plast Reconstr Surg. 128:306e–313e. 2011. View Article : Google Scholar : PubMed/NCBI
10	Cho YS, Jeon JH, Hong A, Yang HT, Yim H, Cho YS, Kim DH, Hur J, Kim JH, Chun W, et al: The effect of burn rehabilitation massage therapy on hypertrophic scar after burn: A randomized controlled trial. Burns. 40:1513–1520. 2014. View Article : Google Scholar : PubMed/NCBI
11	Azzam OA, Bassiouny DA, El-Hawary MS, El Maadawi ZM, Sobhi RM and El-Mesidy MS: Treatment of hypertrophic scars and keloids by fractional carbon dioxide laser: A clinical, histological, and immunohistochemical study. Laser Med Sci. 31:9–18. 2016. View Article : Google Scholar
12	O'Brien L and Jones DJ: Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. 9:CD0038262013.
13	Ogawa R, Miyashita T, Hyakusoku H, Akaishi S, Kuribayashi S and Tateno A: Postoperative radiation protocol for keloids and hypertrophic scars: Statistical analysis of 370 sites followed for over 18 months. Ann Plast Surg. 59:688–691. 2007. View Article : Google Scholar : PubMed/NCBI
14	Zouboulis CC: Cryosurgery in dermatology. Hautarzt. 66:834–848. 2015.(In German). View Article : Google Scholar : PubMed/NCBI
15	Zhang Q, Liu LN, Yong Q, Deng JC and Cao WG: Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model. Stem Cell Res Ther. 6:1452015. View Article : Google Scholar : PubMed/NCBI
16	Williams CC and De Groote S: Clinical inquiry: What treatment is best for hypertrophic scars and keloids? J Fam Pract. 60:757–758. 2011.PubMed/NCBI
17	Ledon JA, Savas J, Franca K, Chacon A and Nouri K: Intralesional treatment for keloids and hypertrophic scars: A review. Dermatol Surg. 39:1745–1757. 2013. View Article : Google Scholar : PubMed/NCBI
18	Macintyre L and Baird M: Pressure garments for use in the treatment of hypertrophic scars-a review of the problems associated with their use. Burns. 32:10–15. 2006. View Article : Google Scholar : PubMed/NCBI
19	Mustoe TA, Cooter RD, Gold MH, Hobbs FD, Ramelet AA, Shakespeare PG, Stella M, Téot L, Wood FM and Ziegler UE; International Advisory Panel on Scar Management, : International clinical recommendations on scar management. Plast Reconstr Surg. 110:560–571. 2002. View Article : Google Scholar : PubMed/NCBI
20	Meaume S, Le Pillouer-Prost A, Richert B, Roseeuw D and Vadoud J: Management of scars: Updated practical guidelines and use of silicones. Eur J Dermatol. 24:435–443. 2014.PubMed/NCBI
21	Chaussy C, Brendel W and Schmiedt E: Extracorporeally induced destruction of kidney stones by shock waves. Lancet. 2:1265–1268. 1980. View Article : Google Scholar : PubMed/NCBI
22	Rassweiler J, Rassweiler MC, Frede T and Alken P: Extracorporeal shock wave lithotripsy: An opinion on its future. Indian J Urol. 30:73–79. 2014. View Article : Google Scholar : PubMed/NCBI
23	Valchanou VD and Michailov P: High energy shock waves in the treatment of delayed and nonunion of fractures. Int Orthop. 15:181–184. 1991. View Article : Google Scholar : PubMed/NCBI
24	Maffulli G, Hemmings S and Maffulli N: Assessment of the effectiveness of extracorporeal shock wave therapy (ESWT) for soft tissue injuries (ASSERT): An online database protocol. Transl Med UniSa. 10:46–51. 2014.PubMed/NCBI
25	Speed C: A systematic review of shockwave therapies in soft tissue conditions: Focusing on the evidence. Br J Sports Med. 48:1538–1542. 2014. View Article : Google Scholar : PubMed/NCBI
26	Goertz O, Lauer H, Hirsch T, Ring A, Lehnhardt M, Langer S, Steinau HU and Hauser J: Extracorporeal shock waves improve angiogenesis after full thickness burn. Burns. 38:1010–1018. 2012. View Article : Google Scholar : PubMed/NCBI
27	Dymarek R, Halski T, Ptaszkowski K, Slupska L, Rosinczuk J and Taradaj J: Extracorporeal shock wave therapy as an adjunct wound treatment: A systematic review of the literature. Ostomy Wound Manage. 60:26–39. 2014.PubMed/NCBI
28	Zhao JC, Xian CJ, Yu JA and Shi K: Advancement in the research of effect of extracorporeal shock wave therapy on wound angiogenesis. Chin J Injury Repair Wound Healing. 9:80–84. 2014.(In Chinese).
29	Zhao J, Xue Y, Yu J, Shi K, Xian C and Zhou X: Advances in the research of mechanism of enhancement of wound healing with extracorporeal shock wave therapy. Zhonghua Shao Shang Za Zhi. 31:315–317. 2015.(In Chinese). PubMed/NCBI
30	Fioramonti P, Cigna E, Onesti MG, Fino P, Fallico N and Scuderi N: Extracorporeal shock wave therapy for the management of burn scars. Dermatol Surg. 38:778–782. 2012. View Article : Google Scholar : PubMed/NCBI
31	Cho YS, Joo SY, Cui H, Cho SR, Yim H and Seo CH: Effect of extracorporeal shock wave therapy on scar pain in burn patients: A prospective, randomized, single-blind, placebo-controlled study. Medicine (Baltimore). 95:e45752016. View Article : Google Scholar : PubMed/NCBI
32	Saggini R, Saggini A, Spagnoli AM, Dodaj I, Cigna E, Maruccia M, Soda G, Bellomo RG and Scuderi N: Extracorporeal shock wave therapy: An emerging treatment modality for retracting scars of the hands. Ultrasound Med Biol. 42:185–195. 2016. View Article : Google Scholar : PubMed/NCBI
33	Morris DE, Wu L, Zhao LL, Bolton L, Roth SI, Ladin DA and Mustoe TA: Acute and chronic animal models for excessive dermal scarring: Quantitative studies. Plast Reconstr Surg. 100:674–681. 1997. View Article : Google Scholar : PubMed/NCBI
34	Köse O and Waseem A: Keloids and hypertrophic scars: Are they two different sides of the same coin? Dermatol Surg. 34:336–346. 2008. View Article : Google Scholar : PubMed/NCBI
35	Scott PG, Dodd CM, Tredget EE, Ghahary A and Rahemtulla F: Immunohistochemical localization of the proteoglycans decorin, biglycan and versican and transforming growth factor-beta in human post-burn hypertrophic and mature scars. Histopathology. 26:423–431. 1995. View Article : Google Scholar : PubMed/NCBI
36	Shah M, Foreman DM and Ferguson MW: Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. J Cell Sci. 108:985–1002. 1995.PubMed/NCBI
37	Desmoulière A, Geinoz A, Gabbiani F and Gabbiani G: Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 122:103–111. 1993. View Article : Google Scholar : PubMed/NCBI
38	Moulin V, Larochelle S, Langlois C, Thibault I, Lopez-Vallé CA and Roy M: Normal skin wound and hypertrophic scar myofibroblasts have differential responses to apoptotic inductors. J Cell Physiol. 198:350–358. 2004. View Article : Google Scholar : PubMed/NCBI
39	Kopp J, Preis E, Said H, Hafemann B, Wickert L, Gressner AM, Pallua N and Dooley S: Abrogation of transforming growth factor-beta signaling by SMAD7 inhibits collagen gel contraction of human dermal fibroblasts. J Biol Chem. 280:21570–21576. 2005. View Article : Google Scholar : PubMed/NCBI
40	Xu J, Lamouille S and Derynck R: TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 19:156–172. 2009. View Article : Google Scholar : PubMed/NCBI
41	Schmierer B and Hill CS: TGFbeta-SMAD signal transduction: Molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 8:970–982. 2007. View Article : Google Scholar : PubMed/NCBI
42	Massagué J: How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 1:169–178. 2000. View Article : Google Scholar : PubMed/NCBI
43	Arno AI, Gauglitz GG, Barret JP and Jeschke MG: New molecular medicine-based scar management strategies. Burns. 40:539–551. 2014. View Article : Google Scholar : PubMed/NCBI
44	Annes JP, Munger JS and Rifkin DB: Making sense of latent TGFbeta activation. J Cell Sci. 116:217–224. 2003. View Article : Google Scholar : PubMed/NCBI
45	Chen W, Fu X, Sun T, Sun X, Zhao Z and Sheng Z: Change of gene expression of transforming growth factor-beta1, Smad 2 and Smad 3 in hypertrophic scars skins. Zhonghua Wai Ke Za Zhi. 40:17–19. 2002.(In Chinese). PubMed/NCBI
46	Wu C, Jiang J, Boye A, Jiang Y and Yang Y: Compound Astragalus and Salvia miltiorrhiza extract suppresses rabbits' hypertrophic scar by modulating the TGF-β/Smad signal. Dermatology. 229:363–368. 2014. View Article : Google Scholar : PubMed/NCBI
47	Bai X, He T, Liu J, Wang Y, Fan L, Tao K, Shi J, Tang C, Su L and Hu D: Loureirin B inhibits fibroblast proliferation and extracellular matrix deposition in hypertrophic scar via TGF-β/Smad pathway. Exp Dermatol. 24:355–360. 2015. View Article : Google Scholar : PubMed/NCBI
48	Wang X, Chu J, Wen CJ, Fu SB, Qian YL, Wo Y, Wang C and Wang DR: Functional characterization of TRAP1-like protein involved in modulating fibrotic processes mediated by TGF-β/Smad signaling in hypertrophic scar fibroblasts. Exp Cell Res. 332:202–211. 2015. View Article : Google Scholar : PubMed/NCBI
49	Schultze-Mosgau S, Blaese MA, Grabenbauer G, Wehrhan F, Kopp J, Amann K, Rodemann HP and Rödel F: Smad-3 and Smad-7 expression following anti-transforming growth factor beta 1 (TGFbeta1)-treatment in irradiated rat tissue. Radiother Oncol. 70:249–259. 2004. View Article : Google Scholar : PubMed/NCBI
50	Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, Mizel DE, Anzano M, Greenwell-Wild T, Wahl SM, Deng C and Roberts AB: Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol. 1:260–266. 1999. View Article : Google Scholar : PubMed/NCBI