Biomechanical strain-induced modulation of proliferation coincides with an ERK1/2-independent nuclear YAP localization.
Exp Cell Res
; 361(1): 93-100, 2017 12 01.
Article
em En
| MEDLINE
| ID: mdl-29017756
ABSTRACT
Biomechanical strain induces activation of the transcriptional co-activator yes-associated protein (YAP) by nuclear re-distribution. Recent findings indicate that the mechanically responsive mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 1/2 is involved in the amount of nuclear YAP, reflecting its activation. In this context, we conducted experiments to detect how biomechanical strain acts on the subcellular localization of YAP in periodontal cells. To this end, cells were subjected to 2.5% static equiaxial strain for different time periods. Western blot and fluorescence imaging-based analyses revealed a clear modulation of nuclear YAP localization. This modulation fairly coincided with the altered course of the KI-67 protein amount in conjunction with the percentage of KI-67-positive and thus proliferating cells. The inhibition of the ERK1/2 activity via U0126 yielded an unchanged strain-related modulation of nuclear YAP localization, while YAP amount in whole cell extracts of strained cells was decreased. Administration of the YAP-inhibiting drug Verteporfin evoked a clear reduction of KI-67-positive and thus proliferating cells by approximately 65%, irrespective of strain. Our data reveal YAP as a regulator of strain-modulated proliferation which occurs in a MAPK-independent fashion.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligamento Periodontal
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Fosfoproteínas
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Núcleo Celular
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Proteína Quinase 1 Ativada por Mitógeno
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Proteína Quinase 3 Ativada por Mitógeno
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Proteínas Adaptadoras de Transdução de Sinal
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Proliferação de Células
Limite:
Humans
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Male
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2017
Tipo de documento:
Article