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• W1889798265 endingPage "701" @default.
• W1889798265 startingPage "694" @default.
• W1889798265 abstract "Lipopolysaccharide (LPS) administration is a model of cholestasis. Organic anion transporting polypeptide 4 (Oatp4; Slc21a10) is almost exclusively expressed in liver. Therefore, it was hypothesized that LPS would down-regulate mouse Oatp4 and that this action is due to a decrease in nuclear binding activity of one or more liver-enriched transcription factors to mouse Oatp4 promoter. The present study indicates a time-dependent decrease in mouse Oatp4 mRNA levels by LPS. Moreover, LPS produced a rapid and profound decrease in nuclear binding activity to the mouse Oatp4 putative response elements for hepatocyte nuclear factor (HNF) 1, CAAT/enhancer binding protein (C/EBP), HNF3, and heterodimers of retinoid X receptor (RXR) and retinoic acid receptor (RAR). Maximal decrease in nuclear binding activity to these response elements preceded a significant reduction of Oatp4 mRNA levels. HNF1alpha bound to the Oatp4 HNF1 response element as a homodimer. Multiple copies of the Oatp4 HNF1alpha response element, inserted upstream of a minimal promoter, were sufficient to mediate reporter activity and responded to the coexpression of HNF1alpha in mouse hepatoma cells. Moreover, HNF1alpha dose dependently activated the Oatp4 promoter (-4.8 kilo-bases to +30 bp). Therefore, HNF1alpha is a potent trans-activator of the mouse Oatp4 promoter. In addition, Oatp4 mRNA levels were markedly decreased (95%) in HNF1alpha-null mice as compared with wild-type mice, suggesting that HNF1alpha levels are critical for the constitutive expression of the Oatp4 gene. Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter." @default.
• W1889798265 created "2016-06-24" @default.
• W1889798265 creator A5031810848 @default.
• W1889798265 creator A5076743166 @default.
• W1889798265 date "2004-09-01" @default.
• W1889798265 modified "2023-09-29" @default.
• W1889798265 title "Role of liver-enriched transcription factors in the down-regulation of organic anion transporting polypeptide 4 (oatp4; oatplb2; slc21a10) by lipopolysaccharide." @default.
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• W1889798265 doi "https://doi.org/10.1124/mol.66.3" @default.
• W1889798265 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15322262" @default.
• W1889798265 hasPublicationYear "2004" @default.
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