Evidence mapPaperPMID 22767443Full record

ArticleEMBO molecular medicine2012

miR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity.

Ryan M Allen, Tyler J Marquart, Carolyn J Albert, Frederick J Suchy, David Q-H Wang, Meenakshisundaram Ananthanarayanan, David A Ford, Angel Baldán

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
9.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 156 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Advances in the Regulation of Lipid Metabolism by Non-Coding RNAs.Animals : an open access journal from MDPI · 2025
    Review
  5. ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. MicroRNA regulation of cholesterol metabolism.Annals of the New York Academy of Sciences · 2021
    Review
  15. MicroRNA-mediated regulation of glucose and lipid metabolism.Nature reviews. Molecular cell biology · 2021
    Review
  16. MicroRNAs and Circular RNAs in Lipoprotein Metabolism.Current atherosclerosis reports · 2021
    Review
  17. Review
  18. Review
  19. Article
  20. MicroRNA-33 Inhibits Adaptive Thermogenesis and Adipose Tissue Beiging.Arteriosclerosis, thrombosis, and vascular biology · 2021
    Article

38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Ryan M AllenEdward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO, USA.
Tyler J Marquart
Carolyn J Albert
Frederick J Suchy
David Q-H Wang
Meenakshisundaram Ananthanarayanan
David A Ford
Angel Baldán
Saint Louis University · USChildren's Hospital Colorado · USYale University · US

Funding

Plasmalogen-derived bioactive lipids in atherosclerosisR01HL074214 · SAINT LOUIS UNIVERSITY · 2004 to 2005
$662k
TSQ QUANTUM ESI-MS SURVEYOR BUNDLE: RENAL, HEART, RETINAL, &LUNG DISEASESS10RR019232 · SAINT LOUIS UNIVERSITY · 2004 to 2004
$339k
NCRR NIH HHS RR019232NCRR NIH HHS S10 RR019232NHLBI NIH HHS HL074214NHLBI NIH HHS HL098907NHLBI NIH HHS HL107794NHLBI NIH HHS R01 HL074214NHLBI NIH HHS R01 HL107794NHLBI NIH HHS R21 HL098907NIDDK NIH HHS DK084434NIDDK NIH HHS R01 DK084434
6 · The paper itself

Abstract

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.

Indexed as

Gene Expression RegulationAdenosine TriphosphatasesAnimalsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 11BileCells, CulturedDietHepatocytesLiverMaleMiceMice, Inbred C57BLMicroRNAsModels, BiologicalPhospholipid Transfer ProteinsAbcb11 protein, mouseAdenosine TriphosphatasesAtp8b1 protein, mouseATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily B, Member 11MicroRNAsMirn33 microRNA, mousePhospholipid Transfer ProteinsSimvastatin

Identifiers

PMID22767443
PMCPMC3491822
OpenAlexW2159167853

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.