Publication: Activation of liver X receptors reduces CFTR-mediated Cl- transport in kidney collecting duct cells
Issued Date
2013-05-08
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ISSN
15221466
03636127
03636127
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2-s2.0-84881649808
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Physiology - Renal Physiology. Vol.305, No.4 (2013)
Suggested Citation
Promporn Raksaseri, Varanuj Chatsudthipong, Chatchai Muanprasat, Sunhapas Soodvilai Activation of liver X receptors reduces CFTR-mediated Cl- transport in kidney collecting duct cells. American Journal of Physiology - Renal Physiology. Vol.305, No.4 (2013). doi:10.1152/ajprenal.00579.2012 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/31311
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Title
Activation of liver X receptors reduces CFTR-mediated Cl- transport in kidney collecting duct cells
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Abstract
Liver X receptors (LXRs) are transcription factors belonging to the nuclear receptor super family, which act as regulators of lipid and glucose metabolism. However, LXRs have been shown to regulate the function of transporters in the kidney, including the Na-Pi cotransporter, organic anion transporter, and epithelial Na+channel. In this report, we demonstrated the ability of LXR ligands, both endogenous [22 (R)-hydroxycholesterol] and synthetic (T0901317 and GW3965), to reduce CFTR-mediated Cl-secretion in a type I Madin-Darby canine kidney (MDCK) cell line and in murine primary inner medullary collecting duct (IMCD) cells, based on measurements of [Arg8]- vasopressin-induced Cl-current. However, treatment of MDCK cell monolayers with 5 M T0901317 for 24 h did not alter ouabainsenstive current or Na-K-ATPase- protein content. Furthermore, basolateral membranes permeabilization of MDCK cell monolayers still resulted in a decrease in apical Cl-current stimulated by both [Arg8]-vasopressin and 8-cholorophenyl-thio-cAMP, indicating that the factor(s) encoded by the target gene(s) of agonist-activated LXRs might be located at the apical membrane. Western blot analysis revealed that inhibition of Cl-secretion occurred via a decrease in CFTR protein, which was not due to downregulation of its mRNA expression. In addition, both synthetic LXR agonists significantly retarded the growth of forskolin-induced cysts formed in MDCK cells cultured in collagen gel. This is the first evidence showing that ligand-activated LXRs are capable of downregulating CFTR-mediated Cl-secretion of kidney cells and of retarding cyst growth in a MDCK cell model. © 2013 the American Physiological Society.