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藻酸盐凝胶包封的腺病毒表达松弛素对猪模型瘢痕重塑的影响。

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

机构信息

Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Yonsei University College of Medicine, Seoul, Korea.

Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.

出版信息

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

DOI:10.3349/ymj.2019.60.9.854
PMID:31433583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6704020/
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.

摘要

目的

松弛素 (RLX) 是转化生长因子-β1 (TGF-β1) 的拮抗剂，被认为是一种有效的胶原重排剂和细胞外基质成分的主要抑制剂。腺病毒 (Ads) 是癌症基因治疗的公认载体。然而，Ad 的重复治疗受到体内短期生物活性的限制。本研究通过可注射藻酸盐凝胶基质系统评估持续 RLX 表达对瘢痕重塑的疗效。

材料和方法

用载有松弛素的腺病毒 (gel/Ad-RLX) 处理猪瘢痕组织。比较了瘢痕的表面积、颜色和柔韧性，并分析了影响瘢痕形成和胶原排列的各种因素。

结果

gel/Ad-RLX 减少了瘢痕的大小、颜色指数和柔韧性。免疫组化显示，在 gel/Ad-RLX 处理组中主要细胞外基质蛋白的水平降低。此外，gel/Ad-RLX 治疗降低了组织金属蛋白酶抑制剂-1 和α-平滑肌肌动蛋白的表达，显著增加了猪瘢痕组织中基质金属蛋白酶-1 的表达。gel/Ad-RLX 还显著下调了猪瘢痕组织中的 TGF-β1 mRNA，并上调了 TGF-β3 mRNA。

结论

这些结果支持 RLX 在瘢痕重塑中的重要作用，并表明 gel/Ad-RLX 可能对瘢痕形成具有治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/f32b84957d63/ymj-60-854-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/ba6fb182a569/ymj-60-854-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/515acfa3b400/ymj-60-854-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/bbc971a69ae7/ymj-60-854-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/e232d7d25bbb/ymj-60-854-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/f32b84957d63/ymj-60-854-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/ba6fb182a569/ymj-60-854-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/515acfa3b400/ymj-60-854-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/bbc971a69ae7/ymj-60-854-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/e232d7d25bbb/ymj-60-854-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/609c/6704020/f32b84957d63/ymj-60-854-g005.jpg

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