ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Micro-RNA 21 inhibition of SMAD7 enhances fibrogenesis via leptin-mediated NADPH oxidase in experimental and human nonalcoholic steatohepatitis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- The use of circulating miRNAs for the diagnosis, prognosis, and personalized treatment of MASLD.Journal of physiology and biochemistry · 2025Pooled it
- Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Nicotinamide Adenine Dinucleotide Phosphate Oxidases and Metabolic Dysfunction-Associated Steatotic Liver Disease.Antioxidants (Basel, Switzerland) · 2025Review
- MicroRNA: A Novel Class of Potential Biomarkers and Therapeutic Target for Non-Alcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis.MicroRNA (Shariqah, United Arab Emirates) · 2025Review
- Review
- MicroRNAs in chronic pediatric diseases (Review).Experimental and therapeutic medicine · 2024Review
- Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease.Non-coding RNA · 2024Review
- Exosome prospects in the diagnosis and treatment of non-alcoholic fatty liver disease.Frontiers in medicine · 2024Review
- Targeted MicroRNA Profiling Reveals That Exendin-4 Modulates the Expression of Several MicroRNAs to Reduce Steatosis in HepG2 Cells.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
- Article
- Noncoding RNAs as additional mediators of epigenetic regulation in nonalcoholic fatty liver disease.World journal of gastroenterology · 2022Review
- Astaxanthin attenuates hepatic steatosis in high-fat diet-fed rats by suppressing microRNA-21 via transactivation of nuclear factor erythroid 2-related factor 2.Journal of physiology and biochemistry · 2022Article
- Update on genetics and epigenetics in metabolic associated fatty liver disease.Therapeutic advances in endocrinology and metabolism · 2022Review
- Article
- PPARγ attenuates hepatic inflammation and oxidative stress of non‑alcoholic steatohepatitis via modulating the miR‑21‑5p/SFRP5 pathway.Molecular medicine reports · 2021Article
- Therapeutic miR-21 Silencing Reduces Cardiac Fibrosis and Modulates Inflammatory Response in Chronic Chagas Disease.International journal of molecular sciences · 2021Article
- Article
- An Update in Epigenetics in Metabolic-Associated Fatty Liver Disease.Frontiers in medicine · 2021Review
- Advances in Unhealthy Nutrition and Circadian Dysregulation in Pathophysiology of NAFLD.Frontiers in clinical diabetes and healthcare · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatic fibrosis in nonalcoholic steatohepatitis (NASH) is the common pathophysiological process resulting from chronic liver inflammation and oxidative stress. Although significant research has been carried out on the role of leptin-induced NADPH oxidase in fibrogenesis, the molecular mechanisms that connect the leptin-NADPH oxidase axis in upregulation of transforming growth factor (TGF)-β signaling have been unclear. We aimed to investigate the role of leptin-mediated upregulation of NADPH oxidase and its subsequent induction of micro-RNA 21 (miR21) in fibrogenesis. Human NASH livers and a high-fat (60% kcal) diet-fed chronic mouse model, where hepatotoxin bromodichloromethane was used to induce NASH, were used for this study. To prove the role of the leptin-NADPH oxidase-miR21 axis, mice deficient in genes for leptin, p47phox, and miR21 were used. Results showed that wild-type mice and human livers with NASH had increased oxidative stress, increased p47phox expression, augmented NF-κB activation, and increased miR21 levels. These mice and human livers showed increased TGF-β, SMAD2/3-SMAD4 colocalizations in the nucleus, increased immunoreactivity against Col1α, and α-SMA with a concomitant decrease in protein levels of SMAD7. Mice that were deficient in leptin or p47phox had decreased activated NF-κB and miR21 levels, suggesting the role of leptin and NADPH oxidase in inducing NF-κB-mediated miR21 expression. Further miR21 knockout mice had decreased colocalization events of SMAD2/3-SMAD4 in the nucleus, increased SMAD7 levels, and decreased fibrogenesis. Taken together, the studies show the novel role of leptin-NADPH oxidase induction of miR21 as a key regulator of TGF-β signaling and fibrogenesis in experimental and human NASH.
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