Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.
Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.
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DOI：
10.1016/j.brainres.2014.01.013
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发表时间：
2014-03-10
期刊：
影响因子：
2.9
通讯作者：
Yang, Shao-Hua
中科院分区：
文献类型：
--
作者：
Choudhury, Gourav Roy;Ryou, Myoung-Gwi;Poteet, Ethan;Wen, Yi;He, Runlian;Sun, Fen;Yuan, Fang;Jin, Kunlin;Yang, Shao-Hua
反应性星形胶质细胞增生是星形胶质细胞对所有形式的中枢神经系统（CNS）损伤和疾病的反应的基本特征，其可有益或有害于周围的神经和非神经细胞。尽管进行了广泛的研究，但其分子触发因素在缺血性卒中方面仍然很大程度上未知。在本研究中，我们调查的作用p38丝裂原活化蛋白激酶（MAPK）在星形胶质细胞在体外和体内。在小鼠大脑中动脉闭塞（MCAO）模型中，在胶质瘢痕区观察到p38 MAPK活化，沿着胶质细胞酸性蛋白（GFAP）表达增加。在原代星形胶质细胞培养中，缺氧和划痕损伤诱导的星形胶质细胞增生通过p38抑制和p38 MAPK敲除而减弱。此外，敲除和抑制p38 MAPK也减少星形胶质细胞迁移，但不影响星形胶质细胞增殖。在永久性MCAO的小鼠模型中，在条件性GFAP/p38 MAPK敲除小鼠和同窝小鼠之间没有观察到运动功能恢复和病变体积的显著差异。而GFAP/p38基因敲除小鼠的星形胶质细胞增生明显减少。我们的研究结果表明，p38 MAPK信号通路在缺血性脑卒中诱导的星形胶质细胞增生中起重要作用，因此可能成为控制胶质瘢痕形成的新靶点。
Reactive astrogliosis is an essential feature of astrocytic response to all forms of central nervous system (CNS) injury and disease, which may benefit or harm surrounding neural and non-neural cells. Despite extensive study, its molecular triggers remain largely unknown in term of ischemic stroke. In the current study we investigated the role p38 mitogen-activated protein kinase (MAPK) in astrogliosis both in vitro and in vivo. In a mouse model of middle cerebral artery occlusion (MCAO), p38 MAPK activation was observed in the glia scar area, along with increased glial fibrillary acidic protein (GFAP) expression. In primary astrocyte cultures, hypoxia and scratch injury-induced astrogliosis was attenuated by both p38 inhibition and knockout of p38 MAPK. In addition, both knockout and inhibition of p38 MAPK also reduced astrocyte migration, but did not affect astrocyte proliferation. In a mouse model of permanent MCAO, no significant difference in motor function recovery and lesion volume was observed between conditional GFAP/p38 MAPK knockout mice and littermates. While a significant reduction of astrogliosis was observed in the GFAP/p38 knockout mice compared with the littermates. Our findings suggest that p38 MAPK signaling pathway plays an important role in the ischemic stroke-induced astrogliosis and thus may serve as a novel target to control glial scar formation.
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影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
DOI：
10.4049/jimmunol.0802954
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brambilla R;Persaud T;Hu X;Karmally S;Shestopalov VI;Dvoriantchikova G;Ivanov D;Nathanson L;Barnum SR;Bethea JR
通讯作者：
Bethea JR
影响因子：
6.3
作者：
Hayakawa, Kazuhide;Nakano, Takafumi;Fujiwara, Michihiro
通讯作者：
Fujiwara, Michihiro
影响因子：
6.2
作者：
Cua, Rowena C.;Lau, Lorraine W.;Yong, V. Wee
通讯作者：
Yong, V. Wee
DOI：
10.1016/s0169-328x(01)00233-9
发表时间：
2001-10-19
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Che, YZ;Yu, YM;Lee, JK
通讯作者：
Lee, JK