MST3 (Mammalian Ste20 Kinase 3) is involved in ENaC-mediated hypertension.

MST3 (Mammalian Ste20 Kinase 3) is involved in ENaC-mediated hypertension. Am J Physiol Renal Physiol. 2019 Apr 10;: Authors: Lu TJ, Kan WC, Yang SS, Jiang ST, Wu SN, Ling P, Bao BY, Lin CY, Yang ZY, Weng YP, Chan CH, Lu TL Abstract Liddle syndrome is an inherited form of human hypertension caused by increasing ENaC (epithelial sodium channel) expression. Increased Na+ retention through ENaC with subsequent volume expansion causes hypertension. In addition to ENaC, NKCC (Na-K-Cl cotransporter) and NCC (Na-Cl symporter) are responsible for Na+ reabsorption in the kidneys. Several Na+ transporters are evolutionarily regulated by the Ste20 kinase family. Ste20-related proline/alanine-rich kinase (SPAK) and oxidative stress-responsive kinase-1 (OSR1) phosphorylate downstream NKCC2 and NCC to maintain Na+ and blood pressure (BP) homeostasis. MST3 is another member of the Ste20 family. We previously reported that reduced MST3 levels were found in the kidneys in spontaneous hypertensive rats and that MST3 was involved in Na+ regulation. To determine whether MST3 is involved in BP stability through Na+ regulation, we generated MST3 hypomorphic mutation and designated MST3 +/- and MST3 -/- mice to examine BP and serum [Na+] and [K+]. The MST3 -/- mice exhibited hypernatremia, hypokalemia and hypertension. The increased ENaC in the kidney played roles in hypernatremia. The reabsorption of more Na+ promoted more K+ secretion in the kidney and c...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research