Transepithelial Fluid and Salt Re-Absorption Regulated by cGK2 Signals

• Main Authors: Jianjun Chang, Yan Ding, Zhiyu Zhou, Hong-Guang Nie, Hong-Long Ji
• Format: Article
• Language: English
• Published: MDPI AG 2018-03-01
• Series: International Journal of Molecular Sciences
• Subjects: fluid and salt re-absorption; epithelial sodium channels; cystic fibrosis transmembrane conductance regulator; protein kinase; acute lung injury
• Online Access: http://www.mdpi.com/1422-0067/19/3/881

Transepithelial fluid and salt re-absorption in epithelial tissues play an important role in fluid and salt homeostasis. In absorptive epithelium, fluid and salt flux is controlled by machinery mainly composed of epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), Na+/H+ exchanger (NHE), aquaporin, and sodium potassium adenosine triphosphatase (Na+/K+-ATPase). Dysregulation of fluid and salt transport across epithelium contributes to the pathogenesis of many diseases, such as pulmonary edema and cystic fibrosis. Intracellular and extracellular signals, i.e., hormones and protein kinases, regulate fluid and salt turnover and resolution. Increasing evidence demonstrates that transepithelial fluid transport is regulated by cyclic guanosine monophosphate-dependent protein kinase (cGK) signals. cGK2 was originally identified and cloned from intestinal specimens, the presence of which has also been confirmed in the kidney and the lung. cGK2 regulates fluid and salt through ENaC, CFTR and NHE. Deficient cGK2 regulation of transepithelial ion transport was seen in acute lung injury, and cGK2 could be a novel druggable target to restore edematous disorder in epithelial tissues.