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Relaxin-Expressing Adenovirus Decreases Collagen Synthesis and Up-Regulates Matrix Metalloproteinase Expression in Keloid Fibroblasts: In Vitro Experiments

Lee, Won Jai M.D., Ph.D.; Choi, Il-Kyu Ph.D.; Lee, Ju Hee M.D., Ph.D.; Lee, Jung-Sun Ph.D.; Kim, Yong Oock M.D., Ph.D.; Rah, Dong Kyun M.D., Ph.D.; Yun, Chae-Ok Ph.D.

doi: 10.1097/PRS.0b013e31825dbf56
Experimental: Original Articles

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.

Seoul, Korea

From the Institute for Human Tissue Restoration, Department of Plastic and Reconstructive Surgery, and the Department of Dermatology, Yonsei University College of Medicine; and the Department of Bioengineering, College of Engineering, Hanyang University.

Received for publication June 30, 2011; accepted March 23, 2012.

Disclosure: The authors have no financial interests or commercial associations to declare in relation to the content of this article.

Chae-Ok Yun, Ph.D.; Department of Bioengineering, College of Engineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Korea, chaeok@hanyang.ac.kr

©2012American Society of Plastic Surgeons