Impaired Autophagic Degradation of Transforming Growth Factor-ß-Induced Protein by Macrophages in Lattice Corneal Dystrophy.
Invest Ophthalmol Vis Sci
; 60(4): 978-989, 2019 03 01.
Article
en En
| MEDLINE
| ID: mdl-30884524
ABSTRACT
Purpose:
Lattice corneal dystrophy (LCD) is related to the denaturation of transforming growth factor-ß-induced protein (TGFBIp). Autophagic degradation of the denatured proteins by macrophages is one pathway to remove the denatured proteins. Thus, we investigated the role of autophagy in the degradation of mutant (MU) TGFBIp in macrophages.Methods:
Corneas from participants were observed by slit-lamp photography and subjected to histopathologic and genetic analysis. Wild-type (WT) and MU TGFBIp were recombined and expressed. Macrophages from MU participants were isolated and cocultured with the recombinant TGFBIp. Colocalization of the two molecules was observed by immunofluorescent microscopy. Enzyme-linked immunosorbent assay, Western blotting, and flow cytometry were used to detect changes in molecule expression related to the phenotype and autophagy process.Results:
Fourteen members from a family of 25 were identified as LCD sufferers. Significant TGFBIp aggregates and macrophage infiltration were found only in the corneas of LCD sufferers. Marker accumulation of TGFBIp was found in macrophages exposed to MU TGFBIp even at 5 hours after MU TGFBIp was withdrawn. High expressions of CD68 and CD36 were found in macrophages exposed to WT TGFBIp, but not to MU TGFBIp. Impaired autophagic flux due to defective autophagosome fusion to lysosomes was found in macrophages exposed to MU TGFBIp. Blockage of the autophagic process suppressed the expression of CD68 and CD36 in macrophages exposed to WT TGFBIp to levels similar to those found in macrophages exposed to MU TGFBIp.Conclusions:
Our results suggested that reversion of the defective autophagic process in macrophages may be a therapeutic strategy for patients with LCD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
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Distrofias Hereditarias de la Córnea
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Proteínas de la Matriz Extracelular
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Factor de Crecimiento Transformador beta
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Macrófagos
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Adolescent
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Adult
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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:
Invest Ophthalmol Vis Sci
Año:
2019
Tipo del documento:
Article
País de afiliación:
China