Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model
10.3349/ymj.2019.60.9.854
- Author:
In Sik YUN
1
;
Eunhye KANG
;
Hyo Min AHN
;
Yong Oock KIM
;
Dong Kyun RAH
;
Tai Suk ROH
;
Won Jai LEE
;
Chae Ok YUN
Author Information
1. Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Yonsei University College of Medicine, Seoul, Korea. pswjlee@yuhs.ac
- Publication Type:Original Article
- Keywords:
Gene therapy;
scar remodeling;
relaxin;
adenovirus;
alginate gel;
pig scar model
- MeSH:
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
- From:Yonsei Medical Journal
2019;60(9):854-863
- CountryRepublic of Korea
- Language:English
-
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.
