In order for gas exchange to occur in an optimum fashion, the alveolar space must remain free of fluid. Convincing evidence indicates that active Na+ transport across the alveolar epithelium in vivo contributes to the reabsorption of the fetal fluid and to the maintenance of fluid free alveolar spaces in adult lungs, especially when either alveolar permeability to plasma proteins or lung hydrostatic pressures are increased. Na+ ion reabsorption occurs through the amiloride sensitive epithelial Na+ channels (((( ENaC) and poorly characterized cation channels. Based on the exciting preliminary data presented in this application, we hypothesize that a newly described protein (( ENaC) fundamentally alters the biophysical properties of ((( ENaC-type channels and renders them sensitive to regulation via the cGMP/PKG axis. The main goals of this application are: 1) to fully characterize the biophysical and pharmacological properties of ( ENaC type channels in both Xenopus oocytes and human lung epithelial cells;2) to investigate the regulation of ( ENaC-containing channels by cGMP in oocytes and human alveolar cells;and 3) to assess the contribution of ( ENaC to vectorial Na+ transport across human epithelial cell monolayers mounted in Ussing chambers and mouse lungs in vivo using state-of-the-art biochemical, molecular biological, electrophysiological and physiological techniques. The following specific hypotheses will be tested: 1) ( ENaC-containing homo- and heteromeric channels expressed in Xenopus oocytes have diverse biophysical properties;2) cGMP regulates (ENaC-containing homo- and heteromeric channels but not ((( channels expressed in Xenopus oocytes;and 3) ( ENaC contributes to the non-((( ENaC Na+ currents across primary human alveolar type II (ATII) and H441 monolayers and to alveolar fluid clearance in mouse lungs. The subject matter of this research is timely and important. Results of these studies may form the molecular basis for development of new therapeutic strategies (such as cGMP delivery) to combat pulmonary edema.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Lung Injury, Repair, and Remodeling Study Section (LIRR)
Program Officer
Harabin, Andrea L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Health Center at Tyler
Organized Research Units
United States
Zip Code
Wang, Li-Juan; Li, Na-Na; Xu, Sai-Juan et al. (2018) A new and important relationship between miRNA-147a and PDPK1 in radiotherapy. J Cell Biochem 119:3519-3527
Bai, Yichun; Liu, Yang; Su, Zhenlei et al. (2018) Gene editing as a promising approach for respiratory diseases. J Med Genet 55:143-149
Zhao, Runzhen; Su, Zhenlei; Wu, Jing et al. (2017) Serious adverse events of cell therapy for respiratory diseases: a systematic review and meta-analysis. Oncotarget 8:30511-30523
Li, Yue; Chang, Jianjun; Cui, Yong et al. (2017) Novel mechanisms for crotonaldehyde-induced lung edema. Oncotarget 8:83509-83522
Liu, Cui; Zhu, Li-Li; Xu, Si-Guang et al. (2016) ENaC/DEG in Tumor Development and Progression. J Cancer 7:1888-1891
Ji, Hong-Long; Nie, Hong-Guang; Chang, Yongchang et al. (2016) CPT-cGMP Is A New Ligand of Epithelial Sodium Channels. Int J Biol Sci 12:359-66
Xu, Siguang; Liu, Cui; Ma, Yana et al. (2016) Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development. Biomed Res Int 2016:2190216
Su, Zhenlei; Zhu, Lili; Wu, Jing et al. (2016) Systematic review and meta-analysis of nasal potential difference in hypoxia-induced lung injury. Sci Rep 6:30780
Liu, Yang; Jiang, Bi-Jie; Zhao, Run-Zhen et al. (2016) Epithelial Sodium Channels in Pulmonary Epithelial Progenitor and Stem Cells. Int J Biol Sci 12:1150-4
Cui, Yong; Li, Huiming; Wu, Sihui et al. (2016) Formaldehyde impairs transepithelial sodium transport. Sci Rep 6:35857

Showing the most recent 10 out of 40 publications