Extracellular matrix elasticity modulates TGF-ß-induced p38 activation and myofibroblast transdifferentiation in human tenon fibroblasts.
Invest Ophthalmol Vis Sci
; 52(12): 9149-55, 2011 Nov 25.
Article
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| MEDLINE
| ID: mdl-22058331
PURPOSE: Extracellular matrix and the cytokine TGF-ß influence scar formation in an interdependent fashion. In this study, the impact of extracellular matrix elasticity on TGF-ß-induced signal transduction and myofibroblast transdifferentiation was examined. METHODS: Primary human tenon fibroblasts were seeded on collagen-coated glass coverslips (rigid environment) or collagen or polyacrylamide gels (elastic environment) of different compliance and stimulated with TGF-ß. Myofibroblast transdifferentiation was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis for the marker gene α-smooth muscle actin (SMA), and SMA incorporation into stress fibers was determined by confocal immunofluorescence microscopy. CTGF transcription was assessed by RT-qPCR. Signaling pathways were examined by Western blot using phosphospecific antibodies and by immunofluorescence microscopy. RESULTS: TGF-ß-dependent myofibroblast transdifferentiation was enhanced in a stiff environment. Increasing matrix elasticity attenuated TGF-ß-induced myofibroblast transdifferentiation and the associated CTGF expression. TGF-ß-induced p38 activation was reduced on elastic substrates. CONCLUSIONS: The results suggest that matrix elasticity influences TGF-ß-dependent activation of p38 signaling and subsequent myofibroblast transdifferentiation. Biomechanical cues represent an important determinant of scarring processes. Therefore, cellular signals elicited by mechanotransduction deserve consideration in the design of novel antifibrotic strategies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
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Proteínas Quinasas p38 Activadas por Mitógenos
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Matriz Extracelular
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Transdiferenciación Celular
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Cápsula de Tenon
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Miofibroblastos
Límite:
Humans
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Estados Unidos