KMID : 0311120190600090854
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Yonsei Medical Journal 2019 Volume.60 No. 9 p.854 ~ p.863
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Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model
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Yun In-Sik
Kang Eun-Hye Ahn Hyo-Min Kim Yong-Oock Rah Dong-Kyun Roh Tai-Suk Lee Won-Jai Yun Chae-Ok
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Abstract
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Purpose: Relaxin (RLX) is a transforming growth factor-¥â1 (TGF-¥â1) 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-¥â1 and upregulated TGF-¥â3 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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KEYWORD
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Gene therapy, scar remodeling, relaxin, adenovirus, alginate gel, pig scar model
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