Document Detail

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:  MEDLINE    
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.
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:  2013-04-01     Revised Date:  2014-10-13    
Medline Journal Info:
Nlm Unique ID:  1306050     Medline TA:  Plast Reconstr Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  158e-173e     Citation Subset:  AIM; IM    
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MeSH Terms
Extracellular Matrix / metabolism*
Fibroblasts / metabolism*
HSP27 Heat-Shock Proteins / physiology*
Integrin alpha2beta1 / physiology*
Keloid / metabolism*
Middle Aged
Plasminogen Activator Inhibitor 2 / physiology*
Young Adult
Reg. No./Substance:
0/HSP27 Heat-Shock Proteins; 0/Integrin alpha2beta1; 0/Plasminogen Activator Inhibitor 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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