期刊
YONSEI MEDICAL JOURNAL
卷 60, 期 9, 页码 854-863出版社
YONSEI UNIV COLL MEDICINE
DOI: 10.3349/ymj.2019.60.9.854
关键词
Gene therapy; scar remodeling; relaxin; adenovirus; alginate gel; pig scar model
资金
- Yonsei University College of Medicine [6-2012-0037]
- Hanyang University of Korea [HY-2011-G-2011 00000001880]
- National Research Foundation of Korea [NRF-2018R1D1A1B07042537, 2016M3A9B5942352]
- Brain Korea 21 plus program
- Hanyang University, Seoul, South Korea [22A20130011095]
Purpose: Relaxin (RLX) is a transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 and upregulated TGF-beta 3 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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