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Article

Farnesoid X Receptor Activation Stimulates Organic Cations Transport in Human Renal Proximal Tubular Cells

1
Research Center of Transport Proteins for Medical Innovation, Department of Physiology, Mahidol University, Bangkok 10400, Thailand
2
Excellent Center for Drug Discovery, Mahidol University, Bangkok 10400, Thailand
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6078; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176078
Received: 13 July 2020 / Revised: 10 August 2020 / Accepted: 12 August 2020 / Published: 24 August 2020
Farnesoid X receptor (FXR) is a ligand-activated transcription factor highly expressed in the liver and kidneys. Activation of FXR decreases organic cation transporter (OCT) 1-mediated clearance of organic cation compounds in hepatocytes. The present study investigated FXR regulation of renal clearance of organic cations by OCT2 modulation and multidrug and toxin extrusion proteins (MATEs). The role of FXR in OCT2 and MATEs functions was investigated by monitoring the flux of 3H–MPP+, a substrate of OCT2 and MATEs. FXR agonists chenodeoxycholic acid (CDCA) and GW4064 stimulated OCT2-mediated 3H–MPP+ uptake in human renal proximal tubular cells (RPTEC/TERT1 cells) and OCT2-CHO-K1 cells. The stimulatory effect of CDCA (20 µM) was abolished by an FXR antagonist, Z-guggulsterone, indicating an FXR-dependent mechanism. CDCA increased OCT2 transport activity via an increased maximal transport rate of MPP+. Additionally, 24 h CDCA treatment increased MATEs-mediated 3H-MPP+ uptake. Moreover, CDCA treatment increased the expression of OCT2, MATE1, and MATE2-K mRNA compared with that of the control. OCT2 protein expression was also increased following CDCA treatment. FXR activation stimulates renal OCT2- and MATE1/2-K-mediated cation transports in proximal tubules, demonstrating that FXR plays a role in the regulation of OCT2 and MATEs in renal proximal tubular cells. View Full-Text
Keywords: Nuclear receptor; renal excretion; kidney; drug transporters; bile acids Nuclear receptor; renal excretion; kidney; drug transporters; bile acids
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MDPI and ACS Style

Wongwan, T.; Chatsudthipong, V.; Soodvilai, S. Farnesoid X Receptor Activation Stimulates Organic Cations Transport in Human Renal Proximal Tubular Cells. Int. J. Mol. Sci. 2020, 21, 6078. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176078

AMA Style

Wongwan T, Chatsudthipong V, Soodvilai S. Farnesoid X Receptor Activation Stimulates Organic Cations Transport in Human Renal Proximal Tubular Cells. International Journal of Molecular Sciences. 2020; 21(17):6078. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176078

Chicago/Turabian Style

Wongwan, Teerasak, Varanuj Chatsudthipong, and Sunhapas Soodvilai. 2020. "Farnesoid X Receptor Activation Stimulates Organic Cations Transport in Human Renal Proximal Tubular Cells" International Journal of Molecular Sciences 21, no. 17: 6078. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176078

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