Farnesoid X receptor, hepatocyte nuclear factors 1α and 3β are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene

Ohtsuka, Hideo; Abe, Takaaki; Onogawa, Tohru; Kondo, Noriko; Sato, Takeaki; Oshio, Hiroshi; Mizutamari, Hiroya; Mikkaichi, Tsuyoshi; Oikawa, Masaya; Rikiyama, Toshiki; Katayose, Yu; Unno, Michiaki

doi:10.1007/s00535-006-1784-3

Cited by 35 publications

(25 citation statements)

References 24 publications

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“…HNF1␣ and 1␤ positively regulate OAT1, OAT3, URAT1, OATP1B1, and OATP1B3 by directly binding to and transactivating their promoters (Fig. 23) (Jung et al, 2001;Kikuchi et al, 2006Kikuchi et al, , 2007Ohtsuka et al, 2006;Furihata et al, 2007;Saji et al, 2008). Furthermore, OATP1B1 mRNA levels correlate with HNF1␣ gene expression in livers from adult Japanese subjects (Furihata et al, 2007).…”

Section: F Hepatocyte Nuclear Factorsmentioning

confidence: 94%

“…Inverted repeat response elements are essential for transactivation of the SLCO1B3 and ABCB11 promoters in response to bile acids Jung et al, 2002a). Functional transactivation of the SLCO1B3 gene has been demonstrated in hepatocyte-derived cells incubated with bile acids (Ohtsuka et al, 2006). Furthermore, a polymorphism in the FXR promoter corresponds with reduced hepatic mRNA expression of human OATP1B1 and -1B3 (Marzolini et al, 2007).…”

Section: E Farnesoid X Receptormentioning

confidence: 99%

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Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

2010

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Section: F Hepatocyte Nuclear Factorsmentioning

confidence: 94%

Section: E Farnesoid X Receptormentioning

confidence: 99%

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

2010

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“…Cumulative clinical evidence shows their importance in the hepatic uptake of a variety of drugs, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, angiotensin-converting enzyme inhibitors, angiotensin receptor II antagonists, and cardiac glycosides, thereby affecting the pharmacological activity and/or adverse events (Giacomini et al, 2010;Hagenbuch and Gui, 2008;Maeda and Sugiyama, 2008). Previously, the promoter regions of OATP1B1 and OATP1B3 have been characterized to identify transcription factors responsible for their gene expression (Jung et al, 2001;Ohtsuka et al, 2006). However, the transcription factors, particularly hepatocyte nuclear factor (HNF) 1a, cannot solely account for the liver-specific expression pattern of these transporters, because these transcription factors are also expressed in extrahepatic tissues, where their target genes OATP1B1 and OATP1B3 are not.…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation and Histone Modification Profiles of Mouse Organic Anion Transporting Polypeptides

et al. 2012

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Organic anion transporting polypeptides (rodents, Oatps; human, OATPs) are primarily involved in the transmembrane transportation of a wide range of endogenous and exogenous compounds. Multiple mouse Oatp1 isoforms are closely located on chromosome 6, where each isoform shows distinct tissue distribution; Oatp1b2, Oatp1a6, and Oatp1c1 are expressed exclusively in the liver, kidney, and cerebrum, respectively; Oatp1a1 in the liver and kidney; and Oatp1a4 in the liver and cerebrum. We have identified tissue-dependent differentially methylated region (T-DMR) around the transcriptional start site (TSS) of Oatp1b2, which correlates with its liver-specific expression. Bisulfite sequencing also demonstrated the presence of T-DMRs around the TSS in other Oatp1 genes: CpG dinucleotides at +149 relative to the TSS for Oatp1c1; 248, +101, and +356 for Oatp1a4; 2572 and 2550 for Oatp1a1; and 2122 and +216 for Oatp1a6 were differentially methylated among the liver, kidney, and cerebrum. These methylation profiles were largely consistent with the tissue distribution of Oatp1 mRNAs. Chromatin immunoprecipitation assay revealed that the mRNA expression of Oatp1 genes was accompanied by acetylated histone H3. Human OATP1B1 and OATP1B3 are located on chromosome 12p12 in the OATP1 cluster; both show predominant expression in the liver. These genes also contained T-DMRs that were hypomethylated in the liver, compared with kidney cortex: 2511, 2411, and +92 relative to the TSS for OATP1B1 and 2331, +70, and +73 for OATP1B3. These results suggest that the difference in epigenetic profiles comprising DNA methylation and histone acetylation determines the distinct tissue distribution of Oatp/OATP mRNAs.

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“…As we reported previously, LST-2 gene expression is also positively regulated by bile acids. 47 Our data suggest LST-2 transports LCA into cancer cells and induces the expression of COX-2. Most secondary bile acids are generated in the colon.…”

Section: Discussionmentioning

confidence: 92%

Peroxisome proliferator-activated receptor α activates cyclooxygenase-2 gene transcription through bile acid transport in human colorectal cancer cell lines

et al. 2008

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These results indicate that COX-2 is transcriptionally activated by the addition of LCA, CDCA, and DCA and that LST-2 plays an important role by transporting bile acid to the intracellular space. Moreover, LCA-dependent COX-2 gene activation consists of a transcriptional complex including PPARalpha and CRE-binding protein. Thus, this induction of COX-2 may participate in carcinogenesis and progression of colorectal cancer cells.

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Farnesoid X receptor, hepatocyte nuclear factors 1α and 3β are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene

Abstract: This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta. HNF1alpha and HNF3beta might contribute to its liver-specific expression, and FXR might play a role in its transcriptional activation by bile acids.

Cited by 35 publications

References 24 publications

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

DNA Methylation and Histone Modification Profiles of Mouse Organic Anion Transporting Polypeptides

Peroxisome proliferator-activated receptor α activates cyclooxygenase-2 gene transcription through bile acid transport in human colorectal cancer cell lines

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