MEK/ERK pathway mediates UVB-induced AQP1 downregulation and water permeability impairment in human retinal pigment epithelial cells
MEK/ERK pathway mediates UVB-induced AQP1 downregulation and water permeability impairment in human retinal pigment epithelial cells
复制标题
MEK/ERK 通路介导 UVB 诱导的人视网膜色素上皮细胞 AQP1 下调和水通透性损伤
DOI：
10.3892/ijmm_00000191
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发表时间：
2009-06-01
影响因子：
5.4
通讯作者：
Wan, Yinsheng
中科院分区：
文献类型：
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作者：
Jiang, Qin;Cao, Cong;Wan, Yinsheng
水通道蛋白（Aquaporins，AQP）是一个由13个小分子（分子量约为30 kDa/单体）疏水性膜蛋白组成的家族。水通道蛋白在参与液体转运的各种上皮和内皮细胞中表达。在这里，我们首次证明了AQP 1在培养的人视网膜色素上皮（RPE）细胞（ARPE-19细胞系）中表达。紫外线辐射（UVB）和H2 O2是导致RPE细胞损伤的两个主要因素，它们通过激活MEK/ERK介导AQP 1表达下调。UV和H2 O 2以及AQP 1特异性siRNA敲低可损害ARPE-19细胞的透水性。值得注意的是，用全反式维甲酸预处理可以减弱紫外线和H（2）O（2）诱导的AQP 1下调和水渗透性损害。考虑到水渗透性涉及RPE细胞的多种功能，如细胞连接形成，液体或蛋白质交换和屏障形成，我们的数据阐明了一种新的机制，通过该机制，紫外线辐射和氧化应激诱导眼细胞损伤。我们的研究结果进一步支持了全反式维甲酸可能对紫外线或氧化应激诱导的眼细胞损伤有保护作用的观点。
Aquaporins (AQPs) are a family of 13 small (similar to 30 kDa/monomer), hydrophobic, integral membrane proteins. AQPs are expressed in various epithelial and endothelial cells involved in fluid transport. Here, we demonstrated for the first time that AQP1 is expressed in cultured human retinal pigment epithelial (RPE) cells (ARPE-19 cell line). Ultraviolet radiation (UVB) and H(2)O(2), two major factors causing RPE cell damage, induced AQP1 downregulation which was mediated by MEK/ERK activation. UV and H(2)O(2) as well as AQP1-specific siRNA knockdown impaired water permeability of ARPE-19 cells. Notably, pretreatment with all-trans retinoic acid attenuated UV- and H(2)O(2)-induced AQP1 downregulation and water permeability impairment. Considering that water permeability is involved in multiple functions of RPE cells such as cellular junction formation, fluid or protein exchange and barrier formation, our data elucidated a novel mechanism through which UV radiation and oxidative stress induce eye cell damage. Our results further Support the notion that all-trans retinoic acid might be useful for protection against UV or oxidative stress-induced eye cell damage.