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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/13545
Title: Liver X receptor agonists decrease ENaC-mediated sodium transport in collecting duct cells
Authors: Sunhapas Soodvilai
Zhanjun Jia
Somsak Fongsupa
Varanuj Chatsudthipong
Tianxin Yang
Mahidol University
University of Utah
Sun Yat-Sen University
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 15-Dec-2012
Citation: American Journal of Physiology - Renal Physiology. Vol.303, No.12 (2012)
Abstract: Liver X receptors (LXRs) are nuclear receptors that regulate cholesterol, fatty acid, and glucose metabolism in various tissues. However, the renal action of LXRs is not well understood. Here we investigated the effects of LXR-activating ligands on modulation of epithelial sodium channel (ENaC)-mediated sodium transport in collecting duct cells. Exposure of the M1 cells to the synthetic LXR agonists T0901317 and GW3965 or the natural ligand 22R-hydroxycholesterol for 24 h decreased amiloride-sensitive sodium transport, corresponding with an increase of transepithelial resistance. The inhibition of amiloridesensitive sodium transport after incubation with T0901317 or GW3965 was not mediated by a reduction of Na + /K + -ATPasemediated basolateral sodium transport. On the other hand, T0901317 and GW3965 decreased mRNA abundance and membrane expression of ENaC. Preincubation the monolayer with GW3965 attenuated aldosterone-induced stimulation sodium transport. In primary cultures of collecting duct cells, T0901317 and GW3965 similarly inhibited ENaC transport function as in M1 cells. This is the first evidence showing LXR-activating ligands modulate ENaC-mediated sodium transport in collecting duct cells. These results suggest that LXRs may represent a novel therapeutic target for treatment of conditions with dysregulation of ENaC such as hypertension.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84871283572&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/13545
ISSN: 15221466
03636127
Appears in Collections:Scopus 2011-2015

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