Abstract
Farnesoid X receptor (FXR) is a nuclear transcriptional factor which highly expressed in the liver, intestine, and kidney. Its plays an essential role in regulation of membrane transporters to eliminate endogenous and xenobiotic compounds. The previous study has shown that endogenous ligand, chenodeoxycholic acid (CDCA) induced by cholestasis down‐regulated hepatic organic cation transporter 1 (OCT1) which plays a critical role in the hepatic secretion of organic cations. It is interesting whether FXR activation regulates multidrug and toxin extrusion protein1 (MATE1) and kidney specific MATE2‐K that play an essential role in the renal cationic drugs efflux into the lumen. The present study showed that treatment with 20 μM CDCA, an endogenous ligand of FXR, for 24 hours stimulated MATE1‐ and MATE2‐K‐mediated 3H‐MPP+ transport in human renal proximal tubular cell line (RPTEC/TERT1 cells). The effect of CDCA was abolished by co‐treatment with a FXR antagonist, Z‐guggulsterone. These data indicated that the stimulatory effect of CDCA on MATEs required FXR‐dependent mechanism. Furthermore, treatment RPTEC/TERT1 cells with CDCA at both physiological level (20 mM) and pathophysiological level (cholestasis) (80 μM) increased mRNA expression of MATE1 and MATE2‐K. Taken together, FXR activation up‐regulates mRNA expression of MATE1 and MATE2‐K resulting in increased cation transports in the proximal tubular cells in both physiological and pathological conditions.Support or Funding InformationThe study was supported by the grant from Mahidol UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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