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Up-Regulation of Tension-Related Proteins in Keloids: Knockdown of Hsp27, α2β1-Integrin, and PAI-2 Shows Convincing Reduction of Extracellular Matrix Production.
MedLine Citation:
PMID:  23358011     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: : Keloid disease is a fibroproliferative disorder, with an ill-defined treatment that is characterized by excessive extracellular matrix deposition. Mechanical tension promotes deposition of extracellular matrix and overexpression of tension-related proteins, which is associated with keloid disease. The aim of this study was to investigate the effect of tension-related proteins on extracellular matrix steady-state synthesis in primary keloid fibroblasts.
METHODS: : Keloid fibroblasts (n = 10) and normal skin (n = 4) fibroblast cultures were established from passages 0 to 3. A panel of 21 tension-related genes from microarray data were assessed at mRNA (quantitative reverse-transcriptase polymerase chain reaction) and protein (in-cell Western blotting) levels. Three genes were significantly altered in keloid tissue and fibroblasts, and their functional role was assessed using siRNA knockdown.
RESULTS: : Hsp27, α2β1-integrin, and PAI-2 were significantly up-regulated (p < 0.05)in keloid tissue and fibroblasts compared with normal skin. Hsp27, α2β1-integrin, and PAI-2 expression was inhibited by RNA interference. Both the mRNA and protein levels of Hsp27, α2β1-integrin, and PAI-2 significantly decreased (p < 0.05) in keloid fibroblasts at 48 hours after transfection. After down-regulation of Hsp27, α2β1-integrin, and PAI-2, the expression of intracellular extracellular matrix was significantly reduced (p < 0.05). Water-soluble tetrazolium salt-1 assay showed that transfection of Hsp27, α2β1-integrin, and PAI-2 did not influence the viability/metabolic activity of keloid fibroblasts.
CONCLUSIONS: : This study demonstrates overexpression of key tension-related proteins in keloid tissue and keloid fibroblasts. Knockdown of Hsp27, PAI-2, and α2β1-integrin by RNA interference attenuates the expression of mRNA and protein levels and certain other extracellular matrix molecules.
Authors:
Edna Suarez; Farhatullah Syed; Teresa Alonso-Rasgado; Parthasarathi Mandal; Ardeshir Bayat
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Plastic and reconstructive surgery     Volume:  131     ISSN:  1529-4242     ISO Abbreviation:  Plast. Reconstr. Surg.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1306050     Medline TA:  Plast Reconstr Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  158e-73e     Citation Subset:  AIM; IM    
Affiliation:
Manchester, United Kingdom From Plastic and Reconstructive Surgery Research, School of Translational Medicine, Manchester Institute of Biotechnology, and the Bioengineering Group, School of Mechanical, Aerospace, and Civil Engineering, University of Manchester, and the University Hospital of South Manchester NHS Foundation Trust, Faculty of Medical and Human Sciences, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre.
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