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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/58959
Title: Farnesoid x receptor activation stimulates organic cations transport in human renal proximal tubular cells
Authors: Teerasak Wongwan
Varanuj Chatsudthipong
Sunhapas Soodvilai
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology;Chemical Engineering;Chemistry;Computer Science
Issue Date: 1-Sep-2020
Citation: International Journal of Molecular Sciences. Vol.21, No.17 (2020), 1-13
Abstract: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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 of3H–MPP+, a substrate of OCT2 and MATEs. FXR agonists chenodeoxycholic acid (CDCA) and GW4064 stimulated OCT2-mediated3H–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-mediated3H-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 OCT2and 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.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/58959
metadata.dc.identifier.url: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85089979471&origin=inward
ISSN: 14220067
16616596
Appears in Collections:Scopus 2020

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