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| 1 | Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes显示文摘Background:Keloids are benign fibroproliferative skin lesions that are difficult to treat and become a lifetime predicament for patients.Several treatment modalities have been put forth,but as yet no satisfactory approach to the prevention or treatment of keloids has been identified.The process of epithelial-to-mesenchymal transition(EMT)has been implicated in keloid scarring,as keloid keratinocytes display an EMT-like phenotype.This study investigated the potential of pirfenidone,an antifibrotic agent,to counteract EMT-like alterations in keloid keratinocytes,including gene expression,cell migratory and proliferative functions.Methods:Normal and keloid keratinocytes were isolated from discarded normal skin tissues and from resected keloid tissues,respectively.Cells were quiesced for 24 h without epidermal growth factor DS-Qi1MCDigital and were exposed to transforming growth factor-beta1(TGF-β1;10 ng/mL),with or without pirfenidone(400μg/mL),for an additional 24 h.The effects of pirfenidone on cytotoxicity,cell migration,cell proliferation,and on expression of genes and proteins involved in EMT were assayed.Statistical significance was determined by two-way ANOVA using Sigma Plot.Results:We found that pirfenidone did not elicit any cytotoxic effect at concentrations up to 1000μg/mL.A statistically significant dose-dependent decrease in basal cell proliferation rate was noted in both normal and keloid keratinocytes when exposed to pirfenidone at concentrations ranging from 200 to 1000μg/mL.Pirfenidone significantly decreased basal cell migration in both normal and keloid keratinocytes,but a significant decrease in TGF-β1-induced cell migration was seen only in keloid keratinocytes.Significant inhibition of the expression of TGF-β1-induced core EMT genes,namely hyaluronan synthase 2,vimentin,cadherin-11,and wingless-type MMTV integration site family,member 5A along with fibronectin-1,was observed in both normal and keloid keratinocytes treated with pirfenidone.In addition,the protein levels of vimentin and fibronectin were significantly reduced by pirfenidone(400μg/mL)in both normal and keloid keratinocytes.Conclusions:For the first time,this study shows the efficacy of pirfenidone in inhibiting the EMTlike phenotype in keratinocytes derived from keloids,suggesting that pirfenidone may counteract a critical contributor of keloid progression and recurrence. | Latha Satish Alexander Evdokiou Eleni Geletu Jennifer M.Hahn Dorothy M.Supp | 2020 | Burns & Trauma2020，8，1： | 3 |
| 2 | The role of osteo- clasts and tumour-associated macrophages in osteosarcoma metas- tasis显示文摘 | Endo-Munoz L Evdokiou A Sannders NA | 2012 | Biochim Biophys Acta2012，1826，2： | 1 |
| 3 | Death to the bad guys: targeting cancer via Apo2L/TRAIL 显示文摘 | Bouralexis S Findlay DM Evdokiou A | 2005 | Apoptosis2005，10，1： | 1 |
| 4 | Induction of cell death of human osteogenic sarcoma cells by zoledronic acid resembles anoikis 显示文摘 | Evdokiou A Labrinidis A | 2003 | Bone2003，33，2： | 1 |
| 5 | Chemotherapeutic agents sensitized osteogenic sarcoma cells, but not normal human bone cells, to apo21/trail-induced apoptosis显示文摘 | Evdokiou A Bouralexis S Atkins GJ | 2002 | Int J Cancer2002，99，4： | 1 |
| 6 | Death to the bad guys:Targeting cancer via Apo2L/TRA IL显示文摘 | Bouralexis S Findlay DM Evdokiou A | | 0，，： | 1 |
| 7 | Chemotherapeutic agents sensitize osteogenic sarcoma cells,but not normal human bone cells,to Apo2L/TRAIL-induced apoptosis显示文摘 | Evdokiou A Bouralexis S Atkins GJ | 2002 | Int J Cancer2002，99，4： | 1 |
| 8 | Death to the bad guys:targeting cancer via Apo2L/TRAIL显示文摘 | BOURALEXIS S FINDLAY DM EVDOKIOU A | 2005 | Apoptosis2005，10，1： | 1 |
| 9 | Chemotherapeutic agents sensitize osteogenic sarcoma cells,but not normal human bone cells,to Apo2L/TRAIL-induced apoptosis显示文摘 | Evdokiou A Bouralexis S | 2002 | Int J Cancer2002，99，4： | 1 |
| 10 | Death to the bad guys:targeting cancer via Apo2L/TRAIL显示文摘 | Bouralexis S Findlay DM Evdokiou A | 2005 | Apoptosis2005，10，1： | 1 |
| 11 | Death to the bad guys: Targeting cancer via Apo2L/TRAIL 显示文摘 | Bouralexis S Findlay DM Evdokiou A | 2005 | Apoptosis2005，10，： | 1 |
| 12 | Death to the bad guys: targeting cancer via Apo2L/TRAIL 显示文摘 | Bouralexis S Findlay D M Evdokiou A | 2005 | Apoptosis2005，10，1： | 1 |
| 13 | Death to the bad guys:Targeting cancer via Apo2L/TRAIL显示文摘 | BOURALEXIS S FINDLAY DM EVDOKIOU A | 2005 | Apoptosis2005，10，1： | 1 |
| 14 | Sclerostin is a locally acting regulator of late‐osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE‐ASARM‐dependent mechanism显示文摘 | Gerald J Atkins Peter S Rowe Hui P Lim Katie J Welldon Renee Ormsby Asiri R Wijenayaka Lesya Zelenchuk Andreas Evdokiou David M Findlay | 2011 | J Bone Miner Res2011，，7： | 1 |
| 15 | The role of osteoclasts and turnout-associated macrophages in osteosarcoma metastasis 显示文摘 | Endo-Munoz L Evdokiou A Saunders NA | 2012 | Bio- chim Biophys Acta2012，1826，2： | 1 |
| 16 | Death to the bad guys: targe- ting cancer via Apo2L/TRAIL显示文摘 | Bouralexis S Findlay DM Evdokiou A | 2005 | Apoptosis2005，10，1： | 1 |
| 17 | The role of osteo-clasts and turnout-associated macrophages in osteosarcoma me- tastasis显示文摘 | Endo-Munoz L Evdokiou A Saunders NA | 2012 | Biochim Biophys Acta2012，1826，2： | 1 |
| 18 | Expression of alternatively-spliced MDM2 transcripts in giant cell tumours of bone 显示文摘 | Evdokiou A Atkins GJ Bouralexis S | 2001 | Int J Oncol2001，19，： | 1 |
| 19 | Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells显示文摘 | Nicolaou K A Liapis V Evdokiou A | | 0，，01： | 1 |
| 20 | Induction of cell death of human osteogenic Sarcoma cells zoledronic acid resembles anoikis 显示文摘 | Evdokiou A Labrinidis A Bouralexis S et 01 | 2003 | Bone2003，33，2： | 1 |
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