Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis

Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis

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...

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Autores principales: Feng Gao, Fang Li, Yanying Miao, Lin-Jie Xu, Yuan Zhao, Qian Li, Sheng-Hai Zhang, Jihong Wu, Xing-Huai Sun, Zhongfeng Wang
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/4d741ed90df54a81afe982c0306825bf
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spelling oai:doaj.org-article:4d741ed90df54a81afe982c0306825bf2021-12-02T11:52:31ZInvolvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis10.1038/s41598-017-01557-y2045-2322https://doaj.org/article/4d741ed90df54a81afe982c0306825bf2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01557-yhttps://doaj.org/toc/2045-2322Abstract 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-p38:p38 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.Feng GaoFang LiYanying MiaoLin-Jie XuYuan ZhaoQian LiSheng-Hai ZhangJihong WuXing-Huai SunZhongfeng WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Feng Gao
Fang Li
Yanying Miao
Lin-Jie Xu
Yuan Zhao
Qian Li
Sheng-Hai Zhang
Jihong Wu
Xing-Huai Sun
Zhongfeng Wang
Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis
description 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-p38:p38 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.
format article
author Feng Gao
Fang Li
Yanying Miao
Lin-Jie Xu
Yuan Zhao
Qian Li
Sheng-Hai Zhang
Jihong Wu
Xing-Huai Sun
Zhongfeng Wang
author_facet Feng Gao
Fang Li
Yanying Miao
Lin-Jie Xu
Yuan Zhao
Qian Li
Sheng-Hai Zhang
Jihong Wu
Xing-Huai Sun
Zhongfeng Wang
author_sort Feng Gao
title Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis
title_short Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis
title_full Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis
title_fullStr Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis
title_full_unstemmed Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis
title_sort involvement of the mek-erk/p38-creb/c-fos signaling pathway in kir channel inhibition-induced rat retinal müller cell gliosis
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/4d741ed90df54a81afe982c0306825bf
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