MST3 is involved in ENaC-mediated hypertension

Te Jung Lu, Wei Chih Kan, Sung Sen Yang, Si Tse Jiang, Sheng Nan Wu, Pin Ling, Bo Ying Bao, Chia Yu Lin, Zin Ya Yang, Yui Ping Weng, Chee Hong Chan, Te Ling Lu

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)


Liddle syndrome is an inherited form of human hy-pertension caused by increasing epithelial Na+ channel (ENaC) expression. Increased Na+ retention through ENaC with subsequent volume expansion causes hypertension. In addition to ENaC, the Na+-K+-Cl cotransporter (NKCC) and Na+-Cl symporter (NCC) are responsible for Na+ reabsorption in the kidneys. Several Na+ transporters are evolutionarily regulated by the Ste20 kinase family. Ste20-related pro-line/alanine-rich kinase and oxidative stress-responsive kinase-1 phos-phorylate downstream NKCC2 and NCC to maintain Na+ and blood pressure (BP) homeostasis. Mammalian Ste20 kinase 3 (MST3) is another member of the Ste20 family. We previously reported that reduced MST3 levels were found in the kidneys in spontaneously hypertensive rats and that MST3 was involved in Na+ regulation. To determine whether MST3 is involved in BP stability through Na+ regulation, we generated a MST3 hypomorphic mutation and designated MST3+/‒ and MST3‒/‒ mice to examine BP and serum Na+ and K+ concentrations. 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 caused hypokalemia. The hypernatremia and hypokalemia in MST3‒/‒ mice were significantly reversed by the ENaC inhibitor amiloride, indicating that MST3‒/‒ mice reabsorbed more Na+ through ENaC. Furthermore, Madin-Darby canine kidney cells stably expressing kinase-dead MST3 displayed elevated ENaC currents. Both the in vivo and in vitro results indicated that MST3 maintained Na+ homeostasis through ENaC regulation. We are the first to report that MST3 maintains BP stability through ENaC regulation.

頁(從 - 到)F30-F42
期刊American Journal of Physiology - Renal Physiology
出版狀態Published - 2019

All Science Journal Classification (ASJC) codes

  • 生理學
  • 泌尿科學


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