Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury
Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury
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DOI：
10.1096/fj.06-6848com
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发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Verkman, A. S.
中科院分区：
文献类型：
--
作者：
Auguste, Kurtis I.;Jin, Songwan;Verkman, A. S.
我们先前报道了从水通道蛋白-4缺陷（AQP 4（-/-））小鼠培养的星形胶质细胞在体外比从野生型（AQP 4（-/-））小鼠培养的星形胶质细胞迁移更慢（J. Cell Sci. 2005; 118，5691 - 5698）。在这里，我们调查的迁移荧光标记的AQP 4（-/-）和AQP 4（-/-）星形胶质细胞植入小鼠大脑中，其中定向运动刺激的平面刺伤3毫米远离注射针的轴。细胞注射后两天，我们确定了标记细胞的位置、延伸率和方向。AQP 4（+/+）细胞向穿刺点的迁移大于离开穿刺点的迁移，而AQP 4（-/-）细胞则无此现象。AQP 4（-/-）星形胶质细胞平均向穿刺点移动1.5 mm，而AQP 4（-/-）细胞平均向穿刺点移动0.6 mm。迁移的AQP 4（-/-）细胞中超过25%但< 3%的AQP 4（-/-）细胞出现伸长（轴比> 2.5）。在transwell实验中，AQP 4（-/-）星形胶质细胞迁移速度比AQP 4（-/-）细胞依赖于孔径的方式。在8小时，类似于50%的AQP 4（-/-）细胞迁移通过8 μ m直径的孔，而AQP 4（-/-）细胞的等效迁移被发现为12 μ m直径的孔。这些结果为AQP 4依赖的星形胶质细胞迁移提供了体内证据，并表明AQP 4表达或功能的调节可能会改变胶质瘢痕形成。
We reported previously that astroglia cultured from aquaporin-4-deficient ( AQP4(-/-)) mice migrate more slowly in vitro than those from wild-type ( AQP4(-/-)) mice ( J. Cell Sci. 2005; 118, 5691 - 5698). Here, we investigate the migration of fluorescently labeled AQP4(-/-) and AQP4(-/-) astroglia after implantation into mouse brains in which directional movement was stimulated by a planar stab wound 3 mm away from the axis of the injection needle. Two days after cell injection we determined the location, elongation ratio, and orientation of labeled cells. Migration of AQP4(+/+) but not AQP4(-/-) cells toward the stab was greater than away from the stab. AQP4(-/-) astroglia moved on average 1.5 mm toward the stab compared with 0.6 mm for AQP4(-/-) cells. More than 25% of the migrating AQP4(-/-) cells but < 3% of AQP4(-/-) cells appeared elongated ( axial ratio > 2.5). In transwell assays, AQP4(-/-) astroglia migrated faster than AQP4(-/-) cells in a manner dependent on pore size. At 8 h, similar to 50% of AQP4(-/-) cells migrated through 8-mu m diameter pores, whereas equivalent migration of AQP4(-/-) cells was found for 12-mu m diameter pores. These results provide in vivo evidence for AQP4-dependent astroglial migration and suggest that modulation of AQP4 expression or function might alter glial scarring.