Activation of liver X receptors reduces cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride transport in kidney collecting duct cells.

In this report, we demonstrate the ability of LXR ligands, both endogenous (22(R)-hydroxycholesterol) and synthetic (T0901317 and GW3965), to reduce cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride secretion in Marlin Darby canine kidney (MDCK) cell line and in murine primary inner medullary collecting duct (IMCD) cells, based on measurement of arginine vasopressin (AVP) induced-chloride current (ICl-). However, treatment of MDCK monolayer cells with 5 µM T0901317 for 24 h did not alter ouabain-senstive current or Na+/K+ATPaseα protein content. Furthermore, permeabilization of MDCK monolayer cell basolateral membranes still resulted in a decrease in apical chloride current stimulated by both AVP and 8-cholorophenyl-thio-cAMP (CPT-cAMP), indicating that the factor(s) encoded by the target gene(s) of agonist-activated LXRs might be located at the apical membrane. Western blotting analysis revealed that inhibition of chloride secretion occurred via a decrease in CFTR protein, which was not due to down regulation of its mRNA expression. In addition, both synthetic LXR agonists significantly retard growth of forskolin-induced cysts formed MDCK cells cultured in collagen gel. This is the first evidence showing that ligand-activated LXRs are capable of down-regulating CFTR-mediated chloride secretion of kidney cells and of retarding cyst growth in a MDCK cell model. PMID: 23720350 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research