The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element
Open accessAbstract
Serum levels of HDL are inversely correlated with the risk of coronary heart disease. The anti-atherogenic effect of HDL is partially mediated by its major protein constituent apoA-I. In this study, we identify bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression. Intrahepatocellular accumulation of bile acids, as seen in patients with progressive familial intrahepatic cholestasis and biliary atresia, was associated with diminished apoA-I serum levels. In human apoA-I transgenic mice, treatment with the FXR agonist taurocholic acid strongly decreased serum concentrations and liver mRNA levels of human apoA-I, which was associated with reduced serum HDL levels. Incubation of human primary hepatocytes and hepatoblastoma HepG2 cells with bile acids resulted in a dose-dependent downregulation of apoA-I expression. Promoter mutation analysis and gel-shift experiments in HepG2 cells demonstrated that bile acid-activated FXR decreases human apoA-I promoter activity by a negative FXR response element mapped to the C site. FXR bound this site and repressed transcription in a manner independent of retinoid X receptor. The nonsteroidal synthetic FXR agonist GW4064 likewise decreased apoA-I mRNA levels and promoter activity in HepG2 cells.
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Metadata
- Authors
- Claudel, T., Sturm, E., Duez, H., Torra, I. P., Sirvent, A., Kosykh, V., Fruchart, J.-C., Dallongeville, J., Hum, D. W., Kuipers, F., & Staels, B.
- Venue
- Journal of Clinical Investigation
- Published
- 2002-04-01
- Volume
- 109
- Issue
- 7
- Pages
- 961-971
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2125109896
- Cited by
- 286
- References
- 59
- FWCI
- 19.06
- Type
- journal article
- Language
- en
- Open access
- green
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- Claudel, T., Sturm, E., Duez, H., Torra, I. P., Sirvent, A., Kosykh, V., Fruchart, J.-C., Dallongeville, J., Hum, D. W., Kuipers, F., & Staels, B. (2002). Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. Journal of Clinical Investigation. https://doi.org/10.1172/jci14505
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