Involvement of p38 MAPK in hypotonic stress-induced stimulation of beta- and gamma-ENaC expression in renal epithelium.
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.
Niisato
Naomi
N
Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Taruno
Akiyuki
A
Marunaka
Yoshinori
Y
D000818:Animals; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000096:biosynthesis*; D004848:Epithelium / Q000378:metabolism*; D005786:Gene Expression Regulation; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013312:Stress, Physiological; D015854:Up-Regulation; D014982:Xenopus laevis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D015222:Sodium Channels; D048051:p38 Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole