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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A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
MiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner, K. J., Suárez, Y., Dávalos, A., Parathath, S., Fitzgerald, M. L., Tamehiro, N., Fisher, E. A., Moore, K. J., & Fernández-Hernando, C. (2010) · Science · doi:10.1126/science.1189862 · Cited by 1,260
Han, X., & Gross, R. W. (2004) · Mass Spectrometry Reviews · doi:10.1002/mas.20023 · Cited by 1,126
MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
Najafi-Shoushtari, S. H., Kristo, F., Li, Y., Shioda, T., Cohen, D. E., Gerszten, R. E., & Näär, A. M. (2010) · Science · doi:10.1126/science.1189123 · Cited by 957 · cited 5×
“…that combines statins and anti-miR-33 oligonucleotides may be useful in hyperlipidemic patients by reversing statin-induced, miR-33-mediated repression of ABCA1, which ultimately would increase plasma HDL (Horie et al, 2010; Marquart et al, 2010; Najafi-Shoushtari et al, 2010; Rayner et al, 2010).”
InfluentialDisruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion
Yu, L., Hammer, R. E., Li-Hawkins, J., von Bergmann, K., Lütjohann, D., Cohen, J. C., & Hobbs, H. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252582399 · Cited by 722
Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides
Rayner, K. J., Esau, C. C., Hussain, F. N., McDaniel, A. L., Marshall, S. M., van Gils, J. M., Ray, T. D., Sheedy, F. J., Goedeke, L., Liu, X., et al. (2011) · Nature · doi:10.1038/nature10486 · Cited by 706
Rayner, K. J., Sheedy, F. J., Esau, C. C., Hussain, F. N., Temel, R. E., Parathath, S., van Gils, J. M., Rayner, A. J., Chang, A. N., Suarez, Y., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57275 · Cited by 690 · cited 2×
“Manipulation of miR-33 levels in vivo results in changes in circulating levels of high-density lipoproteins (HDL) (Horie et al, 2010; Marquart et al, 2010; Najafi-Shoushtari et al, 2010; Rayner et al, 2010, 2011a,b).”
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos, A., Goedeke, L., Smibert, P., Ramírez, C. M., Warrier, N. P., Andreo, U., Cirera-Salinas, D., Rayner, K., Suresh, U., Pastor-Pareja, J. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102281108 · Cited by 670
The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis
Rader, D. J., Alexander, E. T., Weibel, G. L., Billheimer, J. T., & Rothblat, G. H. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r800088-jlr200 · Cited by 597
Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo
Wang, X., Collins, H. L., Ranalletta, M., Fuki, I. V., Billheimer, J. T., Rothblat, G. H., Tall, A. R., & Rader, D. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32057 · Cited by 593
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Bile acid signaling in metabolic disease and drug therapy
Li, T., & Chiang, J. Y. L. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008201 · Cited by 935
MicroRNA Regulation of Atherosclerosis
Feinberg, M. W., & Moore, K. J. (2016) · Circulation Research · doi:10.1161/circresaha.115.306300 · Cited by 638
MicroRNA-mediated regulation of glucose and lipid metabolism
Agbu, P., & Carthew, R. W. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00354-w · Cited by 376
MicroRNAs in Metabolic Disease
Fernández-Hernando, C., Ramírez, C. M., Goedeke, L., & Suárez, Y. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.300144 · Cited by 257
MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice
Horie, T., Nishino, T., Baba, O., Kuwabara, Y., Nakao, T., Nishiga, M., Usami, S., Izuhara, M., Sowa, N., Yahagi, N., et al. (2013) · Nature Communications · doi:10.1038/ncomms3883 · Cited by 230
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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