Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1α/PKM2 Signaling Pathway.
Int J Med Sci
; 16(7): 960-966, 2019.
Article
em En
| MEDLINE
| ID: mdl-31341409
ABSTRACT
Background:
Epithelial-to-mesenchymal transition (EMT) is a process whereby epithelial cells lose cell-cell contacts and acquire expression of mesenchymal components and manifest a migratory phenotype. Recent studies indicated that EMT is involved in the development of keloids. Therefore, this study aims to investigate the mechanisms of the effects of metformin in hypoxia-induced EMT in keloid fibroblasts (KFs).Methods:
KFs were cultured in a hypoxia incubator to induce EMT and were treated with or without metformin. Cell viability was evaluated by a cell counting kit 8 (CCK-8), and cell migration was measured by the transwell assay. The expression levels of HIF-1α, E-cadherin, vimentin, phosphorylated p70s6k (p-p70s6k) and pyruvate kinase M2 (PKM2) were evaluated by western blotting.Results:
Hypoxia promoted EMT in KFs. Metformin significantly inhibited the expression of HIF-1α and partially abolished hypoxia-induced EMT. PKM2 is involved in hypoxia-induced EMT of KFs and metformin decreased the expression of p-p70s6k and PKM2.Conclusions:
Metformin abolishes hypoxia-induced EMT in KFs by inhibiting the HIF-1α/PKM2 signaling pathway. Our study provides a novel mechanistic insight into potential use of metformin for treatment of keloids.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Transição Epitelial-Mesenquimal
/
Fibroblastos
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Queloide
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Metformina
Limite:
Adult
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article