Wang, Su (2010)
Ph.D. thesis, University of Birmingham.
Epithelial sodium channels (ENaC) are of immense importance, controlling Na+ transport across epithelia and thus playing a critical role in all aspects of fluid clearance as well as numerous other functions. Although extensive studies have been carried out to invistegate the regulation mechanism of ENaC, many questions still remain unclear. Therefore, we employed various techniques including electrophysiology and molecular biology approaches to investigate the mechanisms underlying the regulation of ENaCs by lipid metabolites, oxygen and mechanical stress. We have identified profound regulation mechanisms of ENaC in distal renal epithelial cells and vascular endothelial cells by lipid metabolites, heme and mechanical forces. Our results revealed a novel O\(_2\) sensitive regulation pathway of ENaC channels, in which hemeoxygenase acts as the O\(_2\) sensor and the substrate and product of which either inhibits or stimulates ENaC activity. This finding may eventually lead to novel clinic strategies in dealing with diseases e.g. renal failure, kidney reperfusion injury, hypertension, pulmonary edema and pre-clampsia. In addition, we, at the first time, have revealed that ENaC is functionally expressed in a variety of endothelial cells and is able to serve as mechano-transducing sensors in the vascular endothelial cells which play important roles in vascular physiology and pathology progresses.
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