Autophagy inhibition attenuates TGF-ß2-induced epithelial-mesenchymal transition in lens epithelial cells.
Life Sci
; 265: 118741, 2021 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-33181173
ABSTRACT
AIMS:
Autophagy has been reported to play an essential role in fibrotic disorders. Known as fibrotic cataract, posterior capsular opacification (PCO) result from pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). This study aims to identify the role and potential mechanism of autophagy in TGF-ß2-induced EMT in LECs. MAINMETHODS:
Primary rabbit LECs were treated with TGF-ß2 to induce EMT as a model of fibrotic cataract in vitro. 3-methyladenine, chloroquine, bafilomycin A1, and gene silencing of autophagy-related protein 7 (ATG7) were treated in LECs for autophagy inhibition, while rapamycin was utilized for autophagy activation. The expression levels of EMT/autophagy-associated markers were analyzed by qRT-PCR, western blotting, immunofluorescence and transmission electron microscopy. We additionally examined cell migration ability with transwell migration assay and wound healing assay. KEYFINDINGS:
TGF-ß2 promoted autophagy flux during EMT progression of LECs in a time-dependent manner. Autophagy activation by rapamycin enhanced TGF-ß2-triggered fibrogenic responses and cell migration in LECs, whereas pharmacological inhibition of autophagy alleviated TGF-ß2-induced increases of EMT markers and cell migration of LECs. In addition, the phosphorylation of Smad2/3 induced by TGF-ß2 was suppressed through autophagy inhibition, while it was promoted upon autophagy activation, indicating that TGF-ß2/Smad signaling was involved in the modulation of autophagy on EMT in LECs. Furthermore, ATG7-silenced LECs exerted anti-fibrosis effect induced by TGF-ß2 through downregulation of autophagy.SIGNIFICANCE:
Intervention/inhibition of autophagy could attenuate TGF-ß2-induced EMT in LECs, which provides autophagy-related insights on preventing and treating the fibrotic cataract or other fibrotic diseases.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta2
/
Cristalino
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article