ArticleCell death & disease2017
miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in mice.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 53 papers, 2 of them syntheses that pooled it.
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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.
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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.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Therapeutic Effects of microRNAs on Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH): A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2023Pooled it
- Investigating microRNAs to Explain the Link between Cholesterol Metabolism and NAFLD in Humans: A Systematic Review.Nutrients · 2022Pooled it
- Article
- MicroRNA-21 is a potential therapeutic agent targetingMolecular therapy. Nucleic acids · 2025Article
- Rewriting the MASLD-associated hepatocellular carcinoma script: Targeting epigenetics and metabolism.International journal of cancer · 2025Review
- Mitochondrial transplantation and platelet rich plasma for the treatment of non-alcoholic fatty liver disease.World journal of hepatology · 2025Review
- miRNAs, lncRNAs, circRNAs and piRNAs in Nonalcoholic Fatty Liver Disease: Past, Present and Future.International journal of molecular sciences · 2025Review
- Obeticholic Acid and Other Farnesoid-X-Receptor (FXR) Agonists in the Treatment of Liver Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Lipophagy and epigenetic alterations are related to metabolic dysfunction-associated steatotic liver disease progression in an experimental model.World journal of hepatology · 2024Article
- miR-21: A therapeutic target for delaying severe liver disease and hepatocellular carcinoma in high-fat-diet-fed mice.bioRxiv : the preprint server for biology · 2024Article
- Hepatic transcriptome discloses the potential targets of Xuefu Zhuyu Decoction ameliorating non-alcoholic fatty liver disease induced by high-fat diet.Journal of traditional and complementary medicine · 2024Article
- [Lithocholic acid decreases mRNA stability of nuclear receptor PPARNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Regulation of hepatic lipid metabolism by intestine epithelium-derived exosomes.Life metabolism · 2023Article
- Hepatic transcriptome delineates the therapeutic effects of Sanren Tang on high-fat diet-induced non-alcoholic fatty liver disease.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Article
- Loss of microRNA-21 protects against acetaminophen-induced hepatotoxicity in mice.Archives of toxicology · 2023Article
- GB1a Activates SIRT6 to Regulate Lipid Metabolism in Mouse Primary Hepatocytes.International journal of molecular sciences · 2023Article
- Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients.International journal of molecular sciences · 2023Article
- Oxidative Stress Modulation by ncRNAs and Their Emerging Role as Therapeutic Targets in Atherosclerosis and Non-Alcoholic Fatty Liver Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Review
Corrections and comments
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- Erratum issued
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
microRNAs were recently suggested to contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a disease lacking specific pharmacological treatments. In that regard, nuclear receptors are arising as key molecular targets for the treatment of nonalcoholic steatohepatitis (NASH). Here we show that, in a typical model of NASH-associated liver damage, microRNA-21 (miR-21) ablation results in a progressive decrease in steatosis, inflammation and lipoapoptosis, with impairment of fibrosis. In a complementary fast food (FF) diet NASH model, mimicking features of the metabolic syndrome, miR-21 levels increase in both liver and muscle, concomitantly with decreased expression of peroxisome proliferator-activated receptor α (PPARα), a key miR-21 target. Strikingly, miR-21 knockout mice fed the FF diet supplemented with farnesoid X receptor (FXR) agonist obeticholic acid (OCA) display minimal steatosis, inflammation, oxidative stress and cholesterol accumulation. In addition, lipoprotein metabolism was restored, including decreased fatty acid uptake and polyunsaturation, and liver and muscle insulin sensitivity fully reinstated. Finally, the miR-21/PPARα axis was found amplified in liver and muscle biopsies, and in serum, of NAFLD patients, co-substantiating its role in the development of the metabolic syndrome. By unveiling that miR-21 abrogation, together with FXR activation by OCA, significantly improves whole body metabolic parameters in NASH, our results highlight the therapeutic potential of nuclear receptor multi-targeting therapies for NAFLD.
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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 OpenQuestion graph.