Aquaporin-1 facilitates epithelial cell migration in kidney proximal tubule
Aquaporin-1 facilitates epithelial cell migration in kidney proximal tubule
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DOI：
10.1681/asn.2005080846
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发表时间：
2006-01-01
影响因子：
13.6
通讯作者：
Verkman, A. S.
中科院分区：
文献类型：
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作者：
Hara-Chikuma, Mariko;Verkman, A. S.
水通道蛋白-1 (AQP1) 是肾近曲小管细胞质膜中主要的水转运蛋白，促进跨上皮水转运。在此，报道了 AQP1 在肾脏中涉及近曲小管细胞迁移的新作用。在野生型和 AQP1 缺失小鼠的近端小管细胞的原代培养物中比较迁移情况。来自 AQP1 缺失小鼠的细胞培养物在外观、生长/增殖和粘附性方面与野生型小鼠的细胞培养物没有区别，尽管正如预期的那样，它们的质膜水渗透性降低了。在博伊登室中存在趋化刺激的情况下测量，与野生型细胞相比，AQP1 缺陷细胞的迁移减少了 > 50%。在伤口愈合的体外划痕试验中也发现 AQP1 缺陷细胞的迁移速度相应减慢，细胞前缘处的片状膜突起的出现减少。在 AQP1 缺陷细胞中，腺病毒介导的 AQP1 表达增加了它们的水渗透性，从而纠正了它们的迁移缺陷。这些体外研究结果与完整肾脏的潜在相关性在肾动脉闭塞 30 分钟引起的急性肾小管损伤的体内模型中进行了测试。缺血再灌注后 3 至 5 天，AQP1 缺失小鼠的肾脏比野生型小鼠的肾脏表现出明显更大的肾小管损伤和细胞肌动蛋白紊乱。这些结果为 AQP1 参与近曲小管细胞迁移以及可能参与近曲小管对损伤的反应提供了证据。
Aquaporin-1 (AQP1) is the principal water-transporting protein in cell plasma membranes in kidney proximal tubule, where it facilitates transepithelial water transport. Here, a novel role for AQP1 in kidney involving the migration of proximal tubule cells is reported. Migration was compared in primary cultures of proximal tubule cells from wild-type and AQP1 null mice. Cell cultures from AQP1 null mice were indistinguishable from those of wild-type mice in their appearance, growth/proliferation, and adhesiveness, although, as expected, they had reduced plasma membrane water permeability. Migration of AQP1-deficient cells was reduced by > 50% compared with wild-type cells, as measured in a Boyden chamber in the presence of a chemotactic stimulus. Comparable slowing of migration of AQP1-deficient cells was also found in an in vitro scratch assay of wound healing, with reduced appearance of lamella-like membrane protrusions at the cell leading edge. Adenoviral-mediated expression of AQP1 in the AQP1-deficient cells, which increased their water permeability to that of wild-type cells, corrected their migration defect. The potential relevance of these in vitro findings to the intact kidney was tested in an in vivo model of acute tubular injury caused by 30 min of renal artery occlusion. At 3 to 5 d after ischemia-reperfusion, kidneys in AQP1 null mice showed remarkably greater tubular injury and cellular actin disorganization than kidneys in wild-type mice. These results provide evidence for the involvement of AQP1 in migration of proximal tubule cells and possibly in the response of the proximal tubule to injury.