Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes

Latha Satish; Alexander Evdokiou; Eleni Geletu; Jennifer M Hahn; Dorothy M Supp

doi:10.1093/burnst/tkz007

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Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes

更新时间：2022-06-09

- Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes
- Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes
- Burns & Trauma 2020年8卷第1期
- 作者机构：
  
  1. Research Department
  2. Department of Pathology & Laboratory Medicine
  3. Department of Surgery
- 作者简介：
- 基金信息：
  
  This study was possible due to generous funding from a private donor and start-up funds from Shriners Hospitals for Children to support LS research. The study also used funding from a grant awarded from Shriners Hospitals for Children- (grant # 85500-CIN-15) to DMS. The funding bodies did not have any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
- DOI：10.1093/burnst/tkz007
  中图分类号：
- 纸质出版日期：2020，
  
  网络出版日期：2020-2-27，
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Latha Satish, Alexander Evdokiou, Eleni Geletu, 等. Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes[J]. Burns & Trauma, 2020,8(1).

Latha Satish, Alexander Evdokiou, Eleni Geletu, Jennifer M Hahn, Dorothy M Supp, Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes, Burns & Trauma, Volume 8, 2020, tkz007, https://doi.org/10.1093/burnst/tkz007
Latha Satish, Alexander Evdokiou, Eleni Geletu, 等. Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes[J]. Burns & Trauma, 2020,8(1). DOI： 10.1093/burnst/tkz007.

Latha Satish, Alexander Evdokiou, Eleni Geletu, Jennifer M Hahn, Dorothy M Supp, Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes, Burns & Trauma, Volume 8, 2020, tkz007, https://doi.org/10.1093/burnst/tkz007 DOI：

摘要

Abstract

BackgroundKeloids 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.MethodsNormal 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 (400 μg/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.ResultsWe found that pirfenidone did not elicit any cytotoxic effect at concentrations up to 1000 μg/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 1000 μg/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 (400 μg/mL) in both normal and keloid keratinocytes.ConclusionsFor the first time

this study shows the efficacy of pirfenidone in inhibiting the EMT-like phenotype in keratinocytes derived from keloids

suggesting that pirfenidone may counteract a critical contributor of keloid progression and recurrence.

关键词

Keywords

KeloidsEMT genesCell migrationProliferationPirfenidoneFibronectin

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