Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis.
Sci Rep
; 7(1): 1480, 2017 05 03.
Article
en En
| MEDLINE
| ID: mdl-28469203
ABSTRACT
Our previous studies have demonstrated that activation of group I metabotropic glutamate receptors downregulated Kir channels in chronic ocular hypertension (COH) rats, thus contributing to Müller cell gliosis, characterized by upregulated expression of glial fibrillary acidic protein (GFAP). In the present study, we explored possible signaling pathways linking Kir channel inhibition and GFAP upregulation. In normal retinas, intravitreal injection of BaCl2 significantly increased GFAP expression in Müller cells, which was eliminated by co-injecting mitogen-activated protein kinase (MAPK) inhibitor U0126. The protein levels of phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2) and its upstream regulator, p-MEK, were significantly increased, while the levels of phosphorylated c-Jun N-terminal kinase (p-JNK) and p38 kinase (p-p38) remained unchanged. Furthermore, the protein levels of phosphorylated cAMP response element binding protein (p-CREB) and c-fos were also increased, which were blocked by co-injecting ERK inhibitor FR180204. In purified cultured rat Müller cells, BaCl2 treatment induced similar changes in these protein levels apart from p-p38 levels and the p-p38p38 ratio showing significant upregulation. Moreover, intravitreal injection of U0126 eliminated the upregulated GFAP expression in COH retinas. Together, these results suggest that Kir channel inhibition-induced Müller cell gliosis is mediated by the MEK-ERK/p38-CREB/c-fos signaling pathway.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Hipertensión Ocular
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Proteína Quinasa 1 Activada por Mitógenos
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Proteína Quinasa 3 Activada por Mitógenos
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Proteínas Quinasas p38 Activadas por Mitógenos
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Gliosis
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article
País de afiliación:
China