Abstract
We studied a role of p38 MAPK in the chronic hypotonicity-stimulated transepithelial Na+ reabsorption in renal epithelial A6 cells. Pretreatment with SB202190 (a specific p38 MAPK inhibitor) drastically decreased the chronic hypotonicity-stimulated transepithelial Na+ reabsorption by reducing the apical Na+ entry through epithelial Na+ channel (ENaC) and the besolateral 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 suppressed the mRNA expression of beta- and gamma-ENaC but not alpha-ENaC. Based on these results, it is suggested that the chronic hypotonicity stimulates the Na+ reabsorption by upregulating the beta- and gamma-ENaC mRNA expression via a p38MAPK-dependent pathway. This work was supported by Grants-in-Aid from Japan Society of The Promotion of Science (17390057, 17590191,18659056, and 19590212), Fuji Foundation for Protein Research, and The Salt Science Research Foundation (0736). [J Physiol Sci. 2008;58 Suppl:S204]
