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; Lee, Ju Hee; Lee, Jung-Sun; Kim, Yong Oock; Rah, Dong Kyun; Yun, Chae-Ok
- Issue Date
- Sep-2012
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Citation
- PLASTIC AND RECONSTRUCTIVE SURGERY, v.130, no.3, pp.407e - 417e
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLASTIC AND RECONSTRUCTIVE SURGERY
- Volume
- 130
- Number
- 3
- Start Page
- 407e
- End Page
- 417e
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/27477
- DOI
- 10.1097/PRS.0b013e31825dbf56
- ISSN
- 0032-1052
- 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)-beta 1 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-beta (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-beta after dE1-RGD/lacZ/RLX transduction, suggesting that relaxin reduces collagen synthesis by blocking TGF-beta 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. (Plast. Reconstr. Surg. 130: 407e, 2012.)
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