Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model
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Purpose: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagenre-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer genetherapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expressionto 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 majorextracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissueinhibitor 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 therapeuticeffects on scar formation.
Abstract
Purpose: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagenre-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer genetherapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expressionto 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 majorextracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissueinhibitor 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 therapeuticeffects on scar formation.
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