miR-184 regulates ezrin, LAMP-1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age-related macular degeneration.
FEBS J
; 281(23): 5251-64, 2014 Dec.
Article
en En
| MEDLINE
| ID: mdl-25251993
ABSTRACT
MicroRNA 184 (miR-184) is known to play a key role in neurological development and apoptosis and is highly expressed in mouse brain, mouse corneal epithelium, zebrafish lens and human retinal pigment epithelium (RPE). However, the role of miR-184 in RPE is largely unknown. We investigated the role of miR-184 in RPE and its possible implication in age-related macular degeneration (AMD). Proteomic analysis identified the ezrin (EZR) gene as a target of miR-184 in human RPE. EZR is a membrane cytoskeleton crosslinker that is also known to bind to lysosomal-associated membrane protein 1 (LAMP-1) during the formation of phagocytic vacuoles. In adult retinal pigment epithelium 19 (ARPE19) cells, inhibition of miR-184 resulted in upregulation of EZR mRNA and EZR protein, and induced downregulation of LAMP-1. The inhibition of miR-184 decreased EZR-bound LAMP-1 protein levels and affected phagocytic activity in ARPE19 cells. In primary culture of human RPE isolated from eyes of AMD donors (AMD RPE), miR-184 was significantly downregulated compared with control (normal) RPE. Downregulation of miR-184 was consistent with significantly lower levels of LAMP-1 protein in AMD RPE, and overexpression of MIR-184 in AMD RPE was able to rescue LAMP-1 protein expression to normal levels. Altogether, these observations suggest a novel role for miR-184 in RPE health and support a model proposing that downregulation of miR-184 expression during aging may result in dysregulation of RPE function, contributing to retinal degeneration.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fagocitosis
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Proteínas del Citoesqueleto
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MicroARNs
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Proteínas de Membrana de los Lisosomas
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Epitelio Pigmentado de la Retina
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Degeneración Macular
Límite:
Adolescent
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Aged
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Aged80
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
FEBS J
Asunto de la revista:
BIOQUIMICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos