Schematic illustration of MRP4 regulation pathway.

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Schematic illustration of MRP4 regulation pathway. Schematic illustration of MRP4 regulation pathway. CAR, PPARα, NFE2-related factor 2 (Nrf2), aryl hydrocarbon receptor (AhR), androgen receptor (AR), estrogen receptor (ER), and farnesoid xenobiotic receptor (FXR) first participate in the control of ABCC4 transcription, although the transcription factors involved are distinct among different cell types and tissues. Moreover, miRNAs suppress MRP4 protein translation through binding to the 3′-untranslated region of mRNA. MRP4 is localized in plasma membrane and can be regulated by internalization through the functions of NHERF1/3 and SNX27. Although MRP4 extrude cAMP outside, the increased cellular cAMP level can decrease MRP4 expression through an exchange proteins activated by cAMP (EPAC)–mediated pathway. In addition, lipid lipoxin A4 and multiwalled carbon nanotubes can downregulate MRP4 through the inhibition of ER and c-Myc, respectively. ANF, atrial natriuretic factor. Jiagen Wen et al. J Pharmacol Exp Ther 2015;354:358-375 Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics