Epigenetic regulation of the epithelial mesenchymal transition induced by synergistic action of TNF-α and TGF-ß in retinal pigment epithelial cells.
Biochem Biophys Res Commun
; 544: 31-37, 2021 03 12.
Article
en En
| MEDLINE
| ID: mdl-33516879
ABSTRACT
To clarify the influence of tumor necrosis factor (TNF)-α on fibrotic phenotypes induced by transforming growth factor (TGF)-ß in retinal pigment epithelial cells (RPECs) by epigenetic regulation. Human primary retinal pigment epithelial cells (RPECs including ARPE19) were used in cultures in the presence or absence of TNF-α and/or TGF-ß2. RT2 Profiler™ (Qiagen) was used for PCR Array for fibrosis and epithelial mesenchymal transition (EMT). Microarray analysis by 3D gene DNA chip was outsourced to Toray Industries Inc. Quantification of histone acetyl transferase (HAT)-related and histone deacetylase (HDAC) related gene expression were also analyzed. HDAC and HAT activity was measured using an EpiQuik HDAC and HAT Activity/Inhibition Assay Kit (Epigentek). CD44, MMP-9, HAT, and HDAC in RPECs were analyzed by western blotting. Analysis of expression of the EMT/fibrosis related CD44 and MMP-9 phenotypes induced by TNF-α+TGF-ß2 revealed four alterations in RPECs 1) abolition of TGF-ß2-induced α-SMA by TNF-α; 2) synergy between TNF-α+TGF-ß2 for induction of CD44 and MMP-9 phenotypes 3) no inhibition of HDAC activity by either TNF-α or TGF-ß2; and 4) significant inhibition of HAT activity by either TNF-α or TGF-ß2, but no synergy. The HDAC activation through HAT inhibition by TNF-α+TGF-ß was counteracted by HDAC inhibitors, leading to the inhibition of EMT/fibrosis. EMT/fibrotic CD44 and MMP-9 phenotypes were epigenetically upregulated by concerted action of TNF-α and TGF-ß in RPECs. The intervention in epigenetic regulation may hold potential in preventing intraocular proliferative diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
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Factor de Necrosis Tumoral alfa
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Epigénesis Genética
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Sinergismo Farmacológico
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Epitelio Pigmentado de la Retina
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Transición Epitelial-Mesenquimal
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón