Transmembrane Serine Protease 2 and Proteolytic Activation of the Epithelial Sodium Channel in Mouse Kidney

Key Points Proteolytic activation of the epithelial sodium channel (ENaC) was compromised by transmembrane serine protease 2 deficiency in murine cortical collecting duct cells and native mouse kidney. To compensate for impaired ENaC activation, rise in plasma aldosterone in response to low-salt diet was enhanced in Tmprss2 −/− mice. Transmembrane serine protease 2 may be a potential drug target to limit proteolytic ENaC activation in disorders with increased renal ENaC activity. Background The renal epithelial sodium channel (ENaC) is essential for sodium balance and BP control. ENaC undergoes complex proteolytic activation by not yet clearly identified tubular proteases. Here, we examined a potential role of transmembrane serine protease 2 (TMPRSS2). Methods Murine ENaC and TMPRSS2 were (co)expressed in Xenopus laevis…