The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
miR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity
Open accessAbstract
Bile secretion is essential for whole body sterol homeostasis. Loss-of-function mutations in specific canalicular transporters in the hepatocyte disrupt bile flow and result in cholestasis. We show that two of these transporters, ABCB11 and ATP8B1, are functional targets of miR-33, a micro-RNA that is expressed from within an intron of SREBP-2. Consequently, manipulation of miR-33 levels in vivo with adenovirus or with antisense oligonucleotides results in changes in bile secretion and bile recovery from the gallbladder. Using radiolabelled cholesterol, we show that systemic silencing of miR-33 leads to increased sterols in bile and enhanced reverse cholesterol transport in vivo. Finally, we report that simvastatin causes, in a dose-dependent manner, profound hepatotoxicity and lethality in mice fed a lithogenic diet. These latter results are reminiscent of the recurrent cholestasis found in some patients prescribed statins. Importantly, pretreatment of mice with anti-miR-33 oligonucleotides rescues the hepatotoxic phenotype. Therefore, we conclude that miR-33 mediates some of the undesired, hepatotoxic effects of statins.
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“the miR-33 family prevents lipid depletion in the liver by targeting genes regulating bile acid synthesis and secretion [ATP-binding cassette subfamily B member 11 (ABCB11), amino phospholipid transporter class I type 8B member 1 (ATP8B1), and cytochrome P450 family 7, subfamily A, polypeptide 1 (CYP7A1) (Allen et al., 2012; Li et al., 2013)].”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Allen et al., 2012
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Metadata
- Authors
- Allen, R. M., Marquart, T. J., Albert, C. J., Suchy, F. J., Wang, D. Q. ‐., Ananthanarayanan, M., Ford, D. A., & Baldán, Á.
- Affiliations
- Saint Louis University (US)
- University of Colorado Anschutz (US)
- Yale University (US)
- Corresponding author
- Baldán, Ángel
- Venue
- EMBO Molecular Medicine
- Published
- 2012-07-05
- Volume
- 4
- Issue
- 9
- Pages
- 882-895
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC3491822
- OpenAlex
- W2159167853
- Cited by
- 159
- References
- 70
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 13 · 2020: 9 · 2019: 10 · 2018: 15 · 2017: 12 · 2016: 16 · 2015: 19 · 2014: 24 · 2013: 18 · 2012: 3
- FWCI
- 20.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EMBO Molecular Medicine (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- AHA (11SDG5030012)
- NIH (HL107794 (to Á.B.), HL074214, HL098907, RR019232)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-33, ABCB11, ATP8B1, simvastatin, lithogenic diet, cholestasis, bile secretion, sterol homeostasis, reverse cholesterol transport, SREBP2, antisense oligonucleotides, gallbladder
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily B, Member 11, Adenosine Triphosphatases, Animals, Bile, Cells, Cultured, Diet, Gene Expression Regulation, Liver, Male, Mice, Inbred C57BL, Models, Biological, ATP-Binding Cassette Transporters, Simvastatin, Hepatocytes, MicroRNAs, Phospholipid Transfer Proteins, Mice
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