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Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model

Authors
 Lee, Won Jai  ;  Lee, Ju Hee  ;  Ahn, Hyo Min  ;  Song, Seung Yong  ;  Kim, Yong Oock  ;  Lew, Dae Hyun  ;  Yun, Chae-Ok 
Citation
 Plastic and Reconstructive Surgery, Vol.136(3) : 328-337, 2015 
Journal Title
 Plastic and Reconstructive Surgery 
ISSN
 0032-1052 
Issue Date
2015
Abstract
BACKGROUND: The 90-kDa heat-shock protein (heat-shock protein 90) is an abundant cytosolic chaperone, and inhibition of heat-shock protein 90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) compromises transforming growth factor (TGF)-β-mediated transcriptional responses by enhancing TGF-β receptor I and II degradation, thus preventing Smad2/3 activation. In this study, the authors evaluated whether heat-shock protein 90 regulates TGF-β signaling in the pathogenesis and treatment of keloids. METHODS: Keloid fibroblasts were treated with 17-AAG (10 μM), and mRNA levels of collagen types I and III were determined by real-time reverse- transcriptase polymerase chain reaction. Also, secreted TGF-β1 was assessed by enzyme-linked immunosorbent assay. The effect of 17-AAG on protein levels of Smad2/3 complex was determined by Western blot analysis. In addition, in 17-AAG-treated keloid spheroids, the collagen deposition and expression of major extracellular matrix proteins were investigated by means of Masson trichrome staining and immunohistochemistry. RESULTS: The authors found that heat-shock protein 90 is overexpressed in human keloid tissue compared with adjacent normal tissue, and 17-AAG decreased mRNA levels of type I collagen, secreted TGF-ß1, and Smad2/3 complex protein expression in keloid fibroblasts. Masson trichrome staining revealed that collagen deposition was decreased in 17-AAG-treated keloid spheroids, and immunohistochemical analysis showed that expression of collagen types I and III, elastin, and fibronectin was markedly decreased in 17-AAG-treated keloid spheroids. CONCLUSION: These results suggest that the antifibrotic action of heat-shock protein 90 inhibitors such as 17-AAG may have therapeutic effects on keloids.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141085
DOI
10.1097/PRS.0000000000001538
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실)
Yonsei Authors
김용욱(Kim, Yong Oock) ; 송승용(Song, Seung Yong) ; 유대현(Lew, Dae Hyun) ; 이원재(Lee, Won Jai) ; 이주희(Lee, Ju Hee)
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