Immunological function of aquaporin-4 in stab-wounded mouse brain in concert with a pro-inflammatory cytokine inducer, osteopontin
Immunological function of aquaporin-4 in stab-wounded mouse brain in concert with a pro-inflammatory cytokine inducer, osteopontin
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DOI：
10.1016/j.mcn.2013.02.002
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发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Yasui, Masato
中科院分区：
文献类型：
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作者：
Ikeshima-Kataoka, Hiroko;Abe, Yoichiro;Yasui, Masato
在中枢神经系统（CNS）损伤期间，星形胶质细胞和小胶质细胞增殖并在损伤部位周围迁移。近年来，水通道蛋白4（aquaporin-4，AQP 4）在脑损伤后星形胶质细胞迁移和胶质瘢痕形成中发挥重要作用，但其分子机制尚不清楚。在本研究中，我们研究了野生型（WT）和AQP 4缺陷（AQP 4/KO）小鼠的大脑皮层刺伤后的表达谱。刺伤后3天，AQP 4的表达在病变部位周围的活化小胶质细胞以及星形胶质细胞中观察到。微阵列分析显示，WT小鼠创伤后3天，损伤部位周围的444个基因上调。令人惊讶的是，大多数这些上调在AQP 4/KO小鼠中显著减弱。实时荧光定量RT-PCR和免疫荧光检测结果显示，AQP 4/KO小鼠骨桥蛋白（OPN）的表达明显低于WT小鼠。此外，在AQP 4/KO小鼠中，促炎细胞因子的上调显著减弱。总之，这些结果表明，AQP 4在CNS病理条件下与OPN一起在免疫功能中起重要作用。(C)2013 Elsevier Inc. All rights reserved.
During injury to the central nervous system (CNS), astrocytes and microglia proliferate and migrate around the lesion sites. Recently, it has been reported that one of the water channels, aquaporin-4 (AQP4) is seemed to have a role in astroglial migration and glial scar formation caused by brain injury, although its molecular mechanism is largely unknown. In the present study, we examined the expression profiles in wild-type (WT) and AQP4-deficient (AQP4/KO) mice after a stab wound to the cerebral cortex. Three days after the stab wound, AQP4 expression was observed in activated microglia around the lesion site as well as in astrocytes. A microarray analysis revealed that 444 genes around the lesion site were upregulated 3 days after the wounding in WT mice. Surprisingly, most of these up-regulations were significantly attenuated in AQP4/KO mice. Real-time RT-PCR and immunofluorescence showed that osteopontin (OPN) expression around the lesion site was much lower in AQP4/KO mice than in WT mice. Moreover, the up-regulation of pro-inflammatory cytokines was significantly attenuated in AQP4/KO mice. Taken together, these results suggest that AQP4 plays an important role in immunological function in concert with OPN under pathological conditions in the CNS. (C) 2013 Elsevier Inc. All rights reserved.