ArticlePloS one2018
miR-122 inhibition in a human liver organoid model leads to liver inflammation, necrosis, steatofibrosis and dysregulated insulin signaling.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- MicroRNAs in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review of Clinical Studies.MicroRNA (Shariqah, United Arab Emirates) · 2025Pooled it
- Redox-sensitive miRNAs and Humanin could mediate effects of exercise and astaxanthin on oxidative stress and inflammation in type 2 diabetes.Scientific reports · 2025Trial
- Evaluation of a human 3D multicellular hepatic spheroid model as a platform for studying hepatic transporters.Cellular and molecular life sciences : CMLS · 2025Article
- The role of liver macrophages in viral liver pathogenesis.Journal of leukocyte biology · 2025Review
- Engineered Hydrogels for Organoid Models of Human Nonalcoholic Fatty Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Modulation of β-Catenin promotes WNT expression in macrophages and mitigates intestinal injury.Cell communication and signaling : CCS · 2025Article
- MicroRNAs as Biomarkers for Metabolic Disorders in Polycystic Ovary Syndrome (PCOS): A Review.Medical science monitor : international medical journal of experimental and clinical research · 2024Review
- β-Carotene Impacts the Liver MicroRNA Profile in a Sex-Specific Manner in Mouse Offspring of Western Diet-Fed Mothers: Results from Microarray Analysis by Direct Hybridization.International journal of molecular sciences · 2024Article
- Ex Vivo Tools and Models in MASLD Research.Cells · 2024Review
- Profile of plasma microRNAs as a potential biomarker of Wilson's disease.Journal of gastroenterology · 2024Article
- Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C.Scientific reports · 2024Article
- Building consensus on the application of organoid-based drug sensitivity testing in cancer precision medicine and drug development.Theranostics · 2024Review
- Placenta mesenchymal stem cell-derived extracellular vesicles alleviate liver fibrosis by inactivating hepatic stellate cells through a miR-378c/SKP2 axis.Inflammation and regeneration · 2023Article
- Organoid Establishment of Long-Term Culture Using Primary Mouse Hepatocytes and Evaluation of Liver Function.Preventive nutrition and food science · 2023Article
- Uncovering Novel Roles of miR-122 in the Pathophysiology of the Liver: Potential Interaction with NRF1 and E2F4 Signaling.Cancers · 2023Article
- NAFLD and AATD Are Two Diseases with Unbalanced Lipid Metabolism: Similarities and Differences.Biomedicines · 2023Review
- The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review).Sovremennye tekhnologii v meditsine · 2023Review
- Advancements in MAFLD Modeling with Human Cell and Organoid Models.International journal of molecular sciences · 2022Review
- Expression profiling of exosomal miRNAs derived from different stages of infection in mice infected with Echinococcus granulosus protoscoleces using high-throughput sequencing.Parasitology research · 2022Article
- NAFLD: Mechanisms, Treatments, and Biomarkers.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To investigate the role of miR-122 in the development and regression of non-alcoholic fatty liver disease (NAFLD) in vitro, we used multicellular 3D human liver organoids developed in our laboratory. These organoids consist of primary human hepatocytes, Kupffer cells, quiescent stellate cells and liver sinusoidal endothelial cells. They remain viable and functional for 4 weeks expressing typical markers of liver function such as synthesis of albumin, urea, and alpha-1 p450 drug metabolism. Before mixing, hepatic cells were transduced with lentivirus to inhibit miR122 expression (ABM, CA). Immediately after the organoids were fully formed (day 4) or after 1 or 2 weeks of additional incubation (days 11 or 18), the organoids were analyzed using fluorescent live/dead staining and ATP production; total RNA was extracted for qPCR gene expression profiling. Our results show that miR-122 inhibition in liver organoids leads to inflammation, necrosis, steatosis and fibrosis. This was associated with increase in inflammatory cytokines (IL6, TNF), chemokines (CCL2, CCL3) and increase in a subset of Matrix Metaloproteinases (MMP8, MMP9). An altered expression of key genes in lipid metabolism (i.e LPL, LDLR) and insulin signaling (i.e GLUT4, IRS1) was also identified.
conclusionOur results highlight the role of miR-122 inhibition in liver inflammation, steatofibrosis and dysregulation of insulin signaling. Patients with NAFLD are known to have altered levels of miR-122, therefore we suggest that miR-122 mimics could play a useful role in reversing liver steatofibrosis and insulin resistance seen in patients with NAFLD.
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Registered trials
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.