P38 inhibition reverses TGFß1 and TNFα-induced contraction in a model of proliferative vitreoretinopathy.
Commun Biol
; 2: 162, 2019.
Article
em En
| MEDLINE
| ID: mdl-31069271
ABSTRACT
Proliferative vitreoretinopathy (PVR) is a metaplasia in the vitreous of the eye manifested by the transformation of retinal pigment epithelial (RPE) cells and the development of contracting epiretinal membranes (ERM), which lead to retinal detachment and vision loss. While TGFß1 and TNFα have been associated with PVR, here we show that these cytokines act synergistically to induce an aggressive contraction phenotype on adult human (ah)RPE. Connected RPE detach upon contraction and form motile membranes that recruit more cells. TGFß1 and TNFα (TNT)-induced contracting membranes uniquely express muscle and extracellular rearrangement genes. Whole transcriptome RNA sequencing of patient-dissected PVR membranes showed activation of the p38-MAPK signaling pathway. Inhibition of p38 during TNT treatment blocks ahRPE transformation and membrane contraction. Furthermore, TNT-induced membrane contractility can be reversed by p38 inhibition after induction. Therefore, targeting the p38-MAPK pathway may have therapeutic benefits for patients with PVR even after the onset of contracting ERMs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Descolamento Retiniano
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Fator de Necrose Tumoral alfa
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Vitreorretinopatia Proliferativa
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Membrana Epirretiniana
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Proteínas Quinases p38 Ativadas por Mitógeno
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Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Aged80
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2019
Tipo de documento:
Article