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Decorin-expressing adenovirus decreases collagen synthesis and upregulates MMP expression in keloid fibroblasts and keloid spheroids

 Won Jai Lee  ;  Hyo Min Ahn  ;  Hyun Roh  ;  Youjin Na  ;  Il-Kyu Choi  ;  Ju Hee Lee  ;  Yong Oock Kim  ;  Dae Hyun Lew  ;  Chae-Ok Yun 
 EXPERIMENTAL DERMATOLOGY, Vol.24(8) : 591-597, 2015 
Journal Title
Issue Date
Adenoviridae/genetics* ; Cells, Cultured ; Collagen Type I/biosynthesis ; Collagen Type I/genetics ; Collagen Type III/biosynthesis ; Collagen Type III/genetics ; Decorin/genetics ; Decorin/therapeutic use* ; Extracellular Matrix Proteins/biosynthesis* ; Extracellular Matrix Proteins/genetics ; Fibroblasts/metabolism* ; Fibroblasts/pathology ; Gene Expression Regulation* ; Genetic Therapy* ; Genetic Vectors/genetics ; Genetic Vectors/pharmacology* ; Humans ; Keloid/metabolism ; Keloid/pathology* ; Matrix Metalloproteinase 1/biosynthesis* ; Matrix Metalloproteinase 1/genetics ; Matrix Metalloproteinase 3/biosynthesis* ; Matrix Metalloproteinase 3/genetics ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Skin/pathology ; Spheroids, Cellular
MMP ; collagen ; decorin-expressing adenovirus ; gene therapy ; keloid ; keloid spheroid
Decorin is a natural transforming growth factor-β1 (TGF-β1) antagonist. Reduced decorin synthesis is associated with dermal scarring, and increased decorin expression appears to reduce scar tissue formation. To investigate the therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and keloid-derived fibroblasts (KFs) were transduced with decorin-expressing adenovirus (dE1-RGD/GFP/DCN), and we examined the therapeutic potential of decorin-expressing Ad for treating pathologic skin fibrosis. Decorin expression was examined by immunofluorescence assay on keloid tissues. HDFs and KFs were transduced with dE1-RGD/GFP/DCN or control virus, and protein levels of decorin, epidermal growth factor receptor (EGFR) and secreted TGF-β1 were assessed by Western blotting and ELISA. And type I and III collagen, and matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3) mRNA levels were measured by real-time RT-PCR. Additionally, we immunohistochemically investigated the expression levels of the major extracellular matrix (ECM) proteins in keloid spheroids transduced with dE1-RGD/GFP/DCN. Lower decorin expression was observed in the keloid region compared to adjacent normal tissues. After treatment with dE1-RGD/GFP/DCN, secreted TGF-β1 and EGFR protein expressions were decreased in TGF-β1-treated HDFs and KFs. Also, type I and III collagen mRNA levels were decreased, and the expression of MMP-1 and MMP-3 mRNA was strongly upregulated. In addition, the expression of type I and III collagen, fibronectin and elastin was significantly reduced in dE1-RGD/GFP/DCN-transduced keloid spheroids. These results support the utility of decorin-expressing adenovirus to reduce collagen synthesis in KFs and keloid spheroid, which may be highly beneficial in treating keloids.
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1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yong Oock(김용욱) ORCID logo https://orcid.org/0000-0002-3756-4809
Lew, Dae Hyun(유대현)
Lee, Won Jai(이원재) ORCID logo https://orcid.org/0000-0003-3056-0503
Lee, Ju Hee(이주희) ORCID logo https://orcid.org/0000-0002-1739-5956
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