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Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model

 In Sik Yun  ;  Eunhye Kang  ;  Hyo Min Ahn  ;  Yong Oock Kim  ;  Dong Kyun Rah  ;  Tai Suk Roh  ;  Won Jai Lee  ;  Chae-Ok Yun 
 Yonsei Medical Journal, Vol.60(9) : 854-863, 2019 
Journal Title
 Yonsei Medical Journal 
Issue Date
Adenoviridae/genetics* ; Adenoviridae/metabolism* ; Alginates* ; Animals ; Cicatrix/metabolism ; Cicatrix/therapy* ; Collagen/metabolism* ; Extracellular Matrix/metabolism ; Matrix Metalloproteinase 1 ; Relaxin/genetics* ; Relaxin/metabolism* ; Relaxin/pharmacology ; Swine ; Tissue Inhibitor of Metalloproteinase-1 ; Transforming Growth Factor beta1
Gene therapy ; adenovirus ; alginate gel ; pig scar model ; relaxin ; scar remodeling
PURPOSE: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. MATERIALS AND METHODS: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. RESULTS: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-β1 and upregulated TGF-β3 mRNAs in pig scar tissues. CONCLUSION: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.
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1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yong Oock(김용욱) ORCID logo https://orcid.org/0000-0002-3756-4809
Rah, Dong Kyun(나동균)
Roh, Tai Suk(노태석) ORCID logo https://orcid.org/0000-0001-8681-159X
Yun, In Sik(윤인식) ORCID logo https://orcid.org/0000-0003-1103-7047
Lee, Won Jai(이원재) ORCID logo https://orcid.org/0000-0003-3056-0503
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