Suppression of EZH2 inhibits TGF-ß1-induced EMT in human retinal pigment epithelial cells.
Exp Eye Res
; 222: 109158, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35780904
ABSTRACT
Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells is critically involved in the occurrence of subretinal fibrosis. This study aimed to investigate the role of enhancer of zeste homolog 2 (EZH2) in EMT of human primary RPE cells and the underlying mechanisms of the anti-fibrotic effect of EZH2 suppression. Primary cultures of human RPE cells were treated with TGF-ß1 for EMT induction. EZH2 was silenced by siRNA to assess the expression levels of epithelial and fibrotic markers using qRT-PCR, Western blot, and immunofluorescence staining assay. Furthermore, the cellular migration, proliferation and barrier function of RPE cells were evaluated. RNA-sequencing analyses were performed to investigate the underlying mechanisms of EZH2 inhibition. Herein, EZH2 silencing up-regulated epithelial marker ZO-1 and downregulated fibrotic ones including α-SMA, fibronectin, and collagen 1, alleviating EMT induced by TGF-ß1 in RPE cells. Moreover, silencing EZH2 inhibited cellular migration and proliferation, but didn't affect cell apoptosis. Additionally, EZH2 suppression contributed to improved barrier functions after TGF-ß1 stimulation. The results from RNA sequencing suggested that the anti-fibrotic effect of EZH2 inhibition was associated with the MAPK signaling pathway, cytokine-cytokine receptor interaction, and the TGF-beta signaling pathway. Our findings provide evidence that the suppression of EZH2 might reverse EMT and maintain the functions of RPE cells. EZH2 could be a potential therapeutic avenue for subretinal fibrosis.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Epiteliales
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Factor de Crecimiento Transformador beta1
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Transición Epitelial-Mesenquimal
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Proteína Potenciadora del Homólogo Zeste 2
Límite:
Humans
Idioma:
En
Revista:
Exp Eye Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
China