Yonsei Med J.  2019 Sep;60(9):854-863. 10.3349/ymj.2019.60.9.854.

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

Affiliations
  • 1Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Yonsei University College of Medicine, Seoul, Korea. pswjlee@yuhs.ac
  • 2Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea. chaeok@hanyang.ac.kr
  • 3Institute of Nano Science and Technology (INST), Hanyang University, Seoul, Korea.
  • 4GeneMedicine Co., Ltd., Seoul, Korea.

Abstract

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.

Keyword

Gene therapy; scar remodeling; relaxin; adenovirus; alginate gel; pig scar model

MeSH Terms

Actins
Adenoviridae*
Cicatrix*
Collagen
Extracellular Matrix
Extracellular Matrix Proteins
Genes, Neoplasm
Genetic Therapy
Immunohistochemistry
Matrix Metalloproteinase 1
Pliability
Relaxin*
RNA, Messenger
Therapeutic Uses
Tissue Inhibitor of Metalloproteinase-1
Actins
Collagen
Extracellular Matrix Proteins
Matrix Metalloproteinase 1
RNA, Messenger
Relaxin
Therapeutic Uses
Tissue Inhibitor of Metalloproteinase-1
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