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Relaxin-expressing adenovirus decreases collagen synthesis and up-regulates matrix metalloproteinase expression in keloid fibroblasts: in vitro experiments

Title
 Relaxin-expressing adenovirus decreases collagen synthesis and up-regulates matrix metalloproteinase expression in keloid fibroblasts: in vitro experiments 
Authors
 Lee, Won Jai ; Choi, Il-Kyu ; Yun, Chae-Ok ; Rah, Dong Kyun ; Kim, Yong Oock ; Lee, Jung-Sun ; Lee, Ju Hee 
Issue Date
2012
Journal Title
 Plastic and Reconstructive Surgery 
ISSN
 0032-1052 
Citation
 Plastic and Reconstructive Surgery, Vol.130(3) : 407e~417e, 2012 
Abstract
BACKGROUND: The hormone relaxin has been shown to affect the extracellular matrix by inhibiting collagen synthesis and expression in fibroblasts stimulated with a profibrotic agent. It also increases matrix metalloproteinase (MMP) expression. To investigate its effect on expression of collagen and MMPs in keloid fibroblasts and human dermal fibroblasts, the authors introduced a relaxin-expressing adenovirus (dE1-RGD/lacZ/RLX) into a human dermal fibroblast cell line and keloid fibroblasts. METHODS: Both fibroblasts were infected with dE1-RGD/lacZ/RLX or control virus, and protein levels of relaxin and secreted transforming growth factor (TGF)-β1 were assessed by enzyme-linked immunosorbent assay, and mRNA levels of collagen type I, collagen type III, MMP-1, and MMP-3 were assessed by real-time reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Expression of Smad3 and phosphorylated Smad3 was also examined, and relaxin's effect on Smad2/3 complex localization was evaluated. RESULTS: When human dermal fibroblasts and keloid fibroblasts were transduced with dE1-RGD/lacZ/RLX or dE1-RGD/lacZ (control), mRNA expression of type I and type III collagen was markedly decreased by relaxin regardless of TGF-β (10 ng/ml) treatment. Expression of Smad3 and phosphorylated Smad3 was reduced in keloid fibroblasts and decreased translocation of Smad 2/3 complex from cytosols to the nucleus of the human dermal fibroblasts with TGF-β after dE1-RGD/lacZ/RLX transduction, suggesting that relaxin reduces collagen synthesis by blocking TGF-β signaling. Analyses revealed that MMP-1 and MMP-3 expression were significantly increased in human dermal fibroblasts and keloid fibroblasts after dE1-RGD/lacZ/RLX transduction. CONCLUSION: These results suggest that the antifibrotic effect of relaxin-expressing adenovirus may have therapeutic effects on keloids.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/91671
DOI
10.1097/PRS.0b013e31825dbf56
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Dermatology
1. 연구논문 > 1. College of Medicine > Dept. of Plastic Surgery & Reconstructive Surgery
Yonsei Authors
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 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00006534-201209000-00007&LSLINK=80&D=ovft
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