Involvement of p38 MAPK in hypotonic stress-induced stimulation of β- and γ-ENaC expression in renal epithelium
Involvement of p38 MAPK in hypotonic stress-induced stimulation of β- and γ-ENaC expression in renal epithelium
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DOI：
10.1016/j.bbrc.2007.04.192
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发表时间：
2007-07-06
影响因子：
3.1
通讯作者：
Marunaka, Yoshinori
中科院分区：
文献类型：
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作者：
Niisato, Naomi;Taruno, Akiyuki;Marunaka, Yoshinori
我们通过慢性应用(20-24小时)低渗(低渗应激)肾上皮A6细胞，研究了p38MAPK在跨跨上皮Na+重吸收调节中的作用。用特异性p38MAPK抑制剂(SB202190)预处理后，尽管限速步骤仍是Na+进入步骤，但通过减少通过顶膜上皮Na+通道(ENaC)的Na+进入和通过Na+/K+ATPase(泵)的Na+排出，可显著减少慢性低张刺激的跨上皮细胞Na+重吸收。我们进一步研究了SB202190对跨上皮Na+重吸收的抑制作用是否通过抑制作为Na+进入途径参与跨上皮Na+重吸收的ENaC的mRNA表达而起作用。慢性低张可增加ENaCα、β和γ亚基的mRNA表达。此外，我们发现SB202190抑制p38MAPK可降低β-和γ-ENaC的mRNA表达，但不影响α-ENaC的表达。基于这些观察，我们认为慢性低张可通过p38 MAPK依赖的途径上调β-和γ-ENaC的mRNA表达来刺激肾跨上皮细胞对Na+的重吸收。(C)2007 Elsevier Inc.保留所有权利。
We investigated a role of p38 MAPK in the regulation of transepithelial Na+ reabsorption by chronic application (20-24 h) of hypotonicity (hypotonic stress) in renal epithelial A6 cells. Pretreatment with a specific p38 MAPK inhibitor (SB202190) significantly reduced the chronic hypotonicity-stimulated transepithelial Na+ reabsorption by diminishing the Na+ entry through epithelial Na+ channel (ENaC) in the apical membrane and the Na+ extrusion via the Na+/K+ ATPase (pump), although the rate limiting step was still the Na+ entry step. We further examined whether the inhibitory effects of SB202190 on the transepithelial Na+ reabsorption is caused through suppression of mRNA expression of ENaC participating in the transepithelial Na+ reabsorption as the Na+ entry pathway. The chronic hypotonicity increased the mRNA expression of alpha-, beta-, and gamma-subunits of ENaC. Moreover, we found that inhibition of p38 MAPK by SB202190 diminished the mRNA expression of beta- and gamma-ENaC but not alpha-ENaC. Based on these observations, it is suggested that the chronic hypotonicity stimulates the renal transepithelial Na+ reabsorption by upregulating the mRNA expression of beta- and gamma-ENaC via a p38 MAPK-dependent pathway. (c) 2007 Elsevier Inc. All rights reserved.