STAT3 signaling after traumatic brain injury
STAT3 signaling after traumatic brain injury
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DOI：
10.1111/j.1471-4159.2011.07610.x
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发表时间：
2012-03-01
影响因子：
4.7
通讯作者：
Atkins, Coleen M.
中科院分区：
文献类型：
--
作者：
Oliva, Anthony A., Jr.;Kang, Yuan;Atkins, Coleen M.
星形胶质细胞通过刺激炎症信号对创伤做出反应。在脑缺血和脊髓损伤的研究中，星形胶质细胞信号传导由细胞因子受体糖蛋白 130 (gp130) 和 Janus 激酶 (Jak) 介导，Janus 激酶 (Jak) 磷酸化转录因子信号转导器和转录激活剂 3 (STAT3)。为了确定 STAT3 在创伤性脑损伤 (TBI) 后是否被激活，成年雄性 SpragueDawley 大鼠接受中度矢状旁液体冲击脑损伤或假手术，然后在长达 7 天的创伤后不同时间段对同侧皮层和海马体进行分析。 Western blot 分析表明，STAT3 磷酸化在 TBI 后 30 分钟显着增加，并持续 24 小时。还观察到 gp130 和 Jak2 磷酸化显着增加。共聚焦显微镜显示 STAT3 主要位于星形细胞核内。 TBI后6小时和24小时，STAT3通路相关基因的表达也增加：细胞因子信号传导抑制因子3、一氧化氮合酶2、集落刺激因子2受体β、制瘤素M、基质金属蛋白酶3、细胞周期蛋白依赖性激酶抑制剂1A、CCAAT/增强子结合蛋白β、白细胞介素2受体γ、白细胞介素4受体a和a-2-巨球蛋白。这些结果阐明了 TBI 后星形胶质细胞中起作用的一些信号通路，并证明 gp130-Jak2-STAT3 信号通路在 TBI 后星形胶质细胞中被激活。
Astrocytes respond to trauma by stimulating inflammatory signaling. In studies of cerebral ischemia and spinal cord injury, astrocytic signaling is mediated by the cytokine receptor glycoprotein 130 (gp130) and Janus kinase (Jak) which phosphorylates the transcription factor signal transducer and activator of transcription-3 (STAT3). To determine if STAT3 is activated after traumatic brain injury (TBI), adult male SpragueDawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery, and then the ipsilateral cortex and hippocampus were analyzed at various post-traumatic time periods for up to 7 days. Western blot analyses indicated that STAT3 phosphorylation significantly increased at 30 min and lasted for 24 h post-TBI. A significant increase in gp130 and Jak2 phosphorylation was also observed. Confocal microscopy revealed that STAT3 was localized primarily within astrocytic nuclei. At 6 and 24 h post-TBI, there was also an increased expression of STAT3 pathway-related genes: suppressor of cytokine signaling 3, nitric oxide synthase 2, colony stimulating factor 2 receptor beta, oncostatin M, matrix metalloproteinase 3, cyclin-dependent kinase inhibitor 1A, CCAAT/enhancer-binding protein beta, interleukin-2 receptor gamma, interleukin-4 receptor a, and a-2-macroglobulin. These results clarify some of the signaling pathways operative in astrocytes after TBI and demonstrate that the gp130-Jak2-STAT3 signaling pathway is activated after TBI in astrocytes.