Involvement of p38 MAPK in hypotonic stress-induced stimulation of beta- and gamma-ENaC expression in renal epithelium.
Involvement of p38 MAPK in hypotonic stress-induced stimulation of beta- and gamma-ENaC expression in renal epithelium.
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发表时间：
2007
影响因子：
3.1
通讯作者：
N. Niisato;Akiyuki Taruno;Y. Marunaka
中科院分区：
文献类型：
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作者：
N. Niisato;Akiyuki Taruno;Y. Marunaka
我们研究了p38 MAPK在慢性低渗（20- 24小时）作用于肾上皮A6细胞调节跨上皮Na（+）重吸收中的作用。用特异性p38 MAPK抑制剂（SB 202190）预处理可显著降低慢性低渗刺激的跨上皮Na（+）重吸收，其机制是减少Na（+）通过上皮Na（+）通道（ENaC）的进入和Na（+）/K（+）ATP酶（泵）的排出，但速率限制步骤仍然是Na（+）进入步骤。我们进一步研究了SB 202190对跨上皮Na（+）重吸收的抑制作用是否是通过抑制作为Na（+）进入途径参与跨上皮Na（+）重吸收的ENaC的mRNA表达而引起的。慢性低渗增加了ENaC α、β和γ亚基的mRNA表达。此外，我们发现SB 202190抑制p38 MAPK降低了β-和γ-ENaC的mRNA表达，但不降低α-ENaC的mRNA表达。基于这些观察结果，提示慢性低渗通过p38 MAPK依赖性途径上调β-和γ-ENaC的mRNA表达，从而刺激肾跨上皮Na（+）重吸收。
We investigated a role of p38 MAPK in the regulation of transepithelial Na(+) reabsorption by chronic application (20-24h) 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.