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Down-regulation of collagen synthesis and matrix metalloproteinase expression in myofibroblasts from dupuytren nodule using adenovirus-mediated relaxin gene therapy

Authors
 Young-Mi Kang  ;  Yun-Rak Choi  ;  Chae-Ok Yun  ;  Jin-Oh Park  ;  Kyung-Soo Suk  ;  Hak-Sun Kim  ;  Moon-Soo Park  ;  Byung-Ho Lee  ;  Hwan-Mo Lee  ;  Seong-Hwan Moon 
Citation
 Journal of Orthopaedic Research, Vol.32(4) : 515-523, 2014 
Journal Title
 Journal of Orthopaedic Research 
ISSN
 0736-0266 
Issue Date
2014
MeSH
Adenoviridae/genetics ; Cells, Cultured ; Collagen/antagonists & inhibitors* ; Collagen/biosynthesis ; Down-Regulation*/genetics ; Dupuytren Contracture/enzymology ; Dupuytren Contracture/metabolism ; Dupuytren Contracture/therapy* ; Fibronectins/metabolism ; Genetic Therapy* ; Humans ; Matrix Metalloproteinases/metabolism* ; Myofibroblasts/metabolism* ; Relaxin/genetics* ; Tissue Inhibitor of Metalloproteinases/antagonists & inhibitors ; Tissue Inhibitor of Metalloproteinases/biosynthesis ; beta-Galactosidase/metabolism
Keywords
Dupuytren's disease ; collagens ; fibrosis ; matrix metalloproteinases ; relaxin
Abstract
Dupuytren's disease is a fibroproliferative connective tissue disorder characterized by contracture of the palmer fascia of the hand. Relaxin (RLN) is a multifunctional factor which contributes to the remodeling of the pelvic ligament by inhibiting fibrosis and inflammatory activities. The aim of this study was to investigate the effect of the RLN gene on the inhibition of fibrosis in myofibroblastic cells. Myofibroblast cells with adenovirus LacZ (Ad-LacZ) as a marker gene or adenovirus relaxin (Ad-RLN) as therapeutic gene showed transgene expressions in beta-galactosidase assay and Western blot analysis. Myofibroblastic cells with Ad-RLN demonstrated a 22% and 48% reduction in collagen I and III mRNA expressions respectively, a 50% decrease in MMP-1, 70% decrease in MMP-2, 80% decrease in MMP-9, and a 15% reduction in MMP-13 protein expression compared with cultures with viral control and saline control. In addition, myofibroblastic cells with Ad-RLN showed a 40% decrease in TIMP 1 and a 15% increase in TIMP 3 protein expression at 48 h compared to cultures with viral control and saline control. Also, myofibroblastic cell with Ad-RLN demonstrated a 74% inhibition of fibronectin and a 52% decrease in total collagen synthesis at 48 h compared with cultures with viral control and saline control. In conclusion, the RLN gene render antifibrogenic effect on myofibroblastic cells from Dupuytren's nodule via direct inhibition of collagen synthesis not through collagenolytic pathway such as MMP-1, -13, TIMP 1, and 3. Therefore relaxin can be an alternative therapeutic strategy in initial stage of Dupuytren's disease by its antifibrogenic effect.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/jor.22535/abstract
DOI
10.1002/jor.22535
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Young Mi(강영미) ORCID logo https://orcid.org/0000-0002-7686-6316
Kim, Hak Sun(김학선) ORCID logo https://orcid.org/0000-0002-8330-4688
Moon, Seong Hwan(문성환)
Park, Jin Oh(박진오)
Suk, Kyung Soo(석경수) ORCID logo https://orcid.org/0000-0003-0633-2658
Lee, Byung Ho(이병호) ORCID logo https://orcid.org/0000-0001-7235-4981
Lee, Hwan Mo(이환모) ORCID logo https://orcid.org/0000-0002-5405-3832
Choi, Yun Rak(최윤락)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98126
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