Biphasic regulation of ENaC by TGF-α and EGF in renal epithelial cells

• Published in: American Journal of Physiology - Renal Physiology 2009-06, Vol.296 (6), p.F1417-F1427
• Main Authors: Liu, Lian, Duke, Billie Jeanne, Malik, Bela, Yue, Qiang, Eaton, Douglas C.
• Format: Article
• Language: English
• ISSN: 1931-857X; 0363-6127; 1522-1466
• DOI: 10.1152/ajprenal.90337.2008

The epithelial sodium channel (ENaC) is regulated by epidermal growth factor (EGF). We investigate whether ENaC is regulated by another EGF receptor (EGFR) ligand, transforming growth factor-α (TGF-α). We show that chronic (24 h) treatment with TGF-α inhibits ENaC in Xenopus laevis kidney cells 20 times more strongly than EGF. By using single-channel measurements, we show that TGF-α significantly reduces the number of ENaC per patch. The open probability ( P o ) is unchanged by 24-h treatment with TGF-α. α-, β-, and γ-ENaC mRNA levels are significantly reduced by TGF-α or EGF. TGF-α or EGF reduces α- and γ-ENaC proteins in the membrane; however, β-ENaC is unchanged. TGF-α or EGF inhibits ENaC by activating EGFR since the EGFR inhibitor AG1478 blocks the effects of both. The MAPK 1/2 inhibitor U0126 also blocks the effect of TGF-α or EGF on ENaC, indicating that the MAPK1/2 pathway is involved in the TGF-α- or EGF-induced inhibition of ENaC. Interestingly, acute treatment (