The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF-κB-TNFα pathway
Open accessAbstract
Background & aims The progression of hepatosteatosis to non-alcoholic steatohepatitis (NASH) is a critical step in the pathogenesis of hepatocellular cancer. However, the underlying mechanism(s) for this progression is essentially unknown. This study was designed to determine the role of miR-378 in regulating NASH progression.Methods We used immunohistochemistry, luciferase assays and immunoblotting to study the role of miR-378 in modulating an inflammatory pathway. Wild-type mice kept on a high-fat diet (HFD) were injected with miR-378 inhibitors or a mini-circle expression system containing miR-378, to study loss and gain-of functions of miR-378.Results MiR-378 expression is increased in livers of dietary obese mice and patients with NASH. Further studies revealed that miR-378 directly targeted Prkag2 that encodes AMP-activated protein kinase γ 2 (AMPKγ2). AMPK signaling negatively regulates the NF-κB-TNFα inflammatory axis by increasing deacetylase activity of sirtuin 1. By targeting Prkag2, miR-378 reduced sirtuin 1 activity and facilitated an inflammatory pathway involving NF-κB-TNFα. In contrast, miR-378 knockdown induced expression of Prkag2, increased sirtuin 1 activity and blocked the NF-κB-TNFα axis. Additionally, knockdown of increased Prkag2 offset the inhibitory effects of miR-378 inhibitor on the NF-κB-TNFα axis, suggesting that AMPK signaling mediates the role of miR-378 in facilitating this inflammatory pathway. Liver-specific expression of miR-378 triggered the development of NASH and fibrosis by activating TNFα signaling. Ablation of TNFα in miR-378-treated mice impaired the ability of miR-378 to facilitate hepatic inflammation and fibrosis, suggesting that TNFα signaling is required for miR-378 to promote NASH.Conclusion MiR-378 plays a key role in the development of hepatic inflammation and fibrosis by positively regulating the NF-κB-TNFα axis. MiR-378 is a potential therapeutic target for the treatment of NASH.Lay summary The recent epidemic of obesity has been associated with a sharp rise in the incidence of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanism(s) remains poorly described and effective therapeutic approaches against NAFLD are lacking. The results establish that microRNA-378 facilitates the development of hepatic inflammation and fibrosis and suggests the therapeutic potential of microRNA-378 inhibitor for the treatment of NAFLD.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The most overexpressed miRNA in patients’ cells was the miR-378-3p, which is considered a modulator of the epithelial-to-mesenchymal transition and is associated with inflammation and fibrosis through the positive modulation of NF-kB and TNFα pathways [167,168].”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [168]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005) · Cell · doi:10.1016/j.cell.2004.12.035 · Cited by 11,855
Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention
Younossi, Z., Anstee, Q. M., Marietti, M., Hardy, T., Henry, L., Eslam, M., George, J., & Bugianesi, E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.109 · Cited by 5,249
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750
Ratziu, V., Harrison, S. A., Francque, S., Bedossa, P., Lehert, P., Serfaty, L., Romero-Gomez, M., Boursier, J., Abdelmalek, M., Caldwell, S., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.038 · Cited by 1,035
Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis
Rolo, A. P., Teodoro, J. S., & Palmeira, C. M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.10.003 · Cited by 955
Nonalcoholic Fatty Liver Disease: Pathology and Pathogenesis
Tiniakos, D. G., Vos, M. B., & Brunt, E. M. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102132 · Cited by 870
Salminen, A., Hyttinen, J. M. T., & Kaarniranta, K. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0748-0 · Cited by 866
IL-6 signal transduction and its physiological roles: the signal orchestration model
Kamimura, D., Ishihara, K., & Hirano, T. (2003) · Reviews of Physiology, Biochemistry and Pharmacology · doi:10.1007/s10254-003-0012-2 · Cited by 673
Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression
Cheung, O., Puri, P., Eicken, C., Contos, M. J., Mirshahi, F., Maher, J. W., Kellum, J. M., Min, H., Luketic, V. A., & Sanyal, A. J. (2008) · Hepatology · doi:10.1002/hep.22569 · Cited by 671
Marrero, J., Fontana, R. J., Su, G. L., Conjeevaram, H. S., Emick, D. M., & Lok, A. S.-F. (2002) · Hepatology · doi:10.1053/jhep.2002.36939 · Cited by 659
From NAFLD to NASH to cirrhosis—new insights into disease mechanisms
Wree, A., Broderick, L., Canbay, A. E., Hoffman, H. M., & Feldstein, A. E. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.149 · Cited by 617
A Human Hepatocellular in Vitro Model to Investigate Steatosis
Gómez-Lechón, M. J., Donato, M. T., Martínez-Romero, A., Jiménez, N., Castell, J. V., & O’Connor, J.-E. (2007) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2006.11.004 · Cited by 576
Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Takahashi, Y. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i19.2300 · Cited by 554
An improved mouse model that rapidly develops fibrosis in non‐alcoholic steatohepatitis
Matsumoto, M., Hada, N., Sakamaki, Y., Uno, A., Shiga, T., Tanaka, C., Ito, T., Katsume, A., & Sudoh, M. (2013) · International Journal of Experimental Pathology · doi:10.1111/iep.12008 · Cited by 523
Treatment of nonalcoholic fatty liver disease: role of AMPK
Smith, B. K., Marcinko, K., Desjardins, E. M., Lally, J., Ford, R. J., & Steinberg, G. R. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00225.2016 · Cited by 511
Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis
Marra, F., Gastaldelli, A., Svegliati‐Baroni, G., Tell, G., & Tiribelli, C. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.003 · Cited by 427
Hepatocyte TAZ/WWTR1 Promotes Inflammation and Fibrosis in Nonalcoholic Steatohepatitis
Wang, X., Zheng, Z., Caviglia, J. M., Corey, K. E., Herfel, T. M., Cai, B., Masia, R., Chung, R. T., Lefkowitch, J. H., Schwabe, R. F., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.016 · Cited by 413
Self-citationPreclinical models of non-alcoholic fatty liver disease
Santhekadur, P. K., Kumar, D. P., & Sanyal, A. J. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.10.031 · Cited by 380
Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*
Carrer, M., Liu, N., Grueter, C. E., Williams, A. H., Frisard, M. I., Hulver, M. W., Bassel‐Duby, R., & Olson, E. N. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207605109 · Cited by 305
Wang, B., Majumder, S., Nuovo, G. J., Kutay, H., Volinia, S., Patel, T. C., Schmittgen, T. D., Croce, C. M., Ghoshal, K., & Jacob, S. T. (2009) · Hepatology · doi:10.1002/hep.23100 · Cited by 305
Xu, Z., Chen, L., Leung, L., Yen, T. S. B., Lee, C., & Chan, J. Y. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500660102 · Cited by 288
Le, M. H., Devaki, P., Ha, N. B., Jun, D. W., Te, H. S., Cheung, R. C., & Nguyen, M. H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173499 · Cited by 287
Cholankeril, G. T., Patel, R., Khurana, S., & Satapathy, S. K. (2017) · World Journal of Hepatology · doi:10.4254/wjh.v9.i11.533 · Cited by 185
Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease
Souza-Mello, V. (2015) · World Journal of Hepatology · doi:10.4254/wjh.v7.i8.1012 · Cited by 182
Sahai, A., Malladi, P., Melin-Aldana, H., Green, R. M., & Whitington, P. F. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00002.2004 · Cited by 181
Non-catalytic - and -Subunit Isoforms of the 5′-AMP-activated Protein Kinase
Gao, G., Fernández, C., Stapleton, D., Auster, A. S., Widmer, J., Dyck, J. R. B., Kemp, B. E., & Witters, L. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8675 · Cited by 129
Use of minicircle plasmids for gene therapy.
Mayrhofer, P., Schleef, M., & Jechlinger, W. (2009) · Methods in molecular biology · doi:10.1007/978-1-59745-561-9_4 · Cited by 125
Liu, W., Cao, H., Cheng, Y., Chang, C., Lü, M., Jing, Y., Zhang, D., Yao, X., Duan, Z., Xia, H., et al. (2014) · Nature Communications · doi:10.1038/ncomms6684 · Cited by 114
Csák, T., Bala, S., Lippai, D., Kodys, K., Catalano, D. E., Iracheta‐Vellve, A., & Szabó, G. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129251 · Cited by 90
Luckett‐Chastain, L. R., & Gallucci, R. M. (2009) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2009.09215.x · Cited by 82
Li, M., Tang, Y., Wu, L., Mo, F., Wang, X., Li, H., Qi, R., Zhang, H., Srivastava, A., & Ling, C. (2017) · Blood · doi:10.1182/blood-2016-12-755967 · Cited by 54
Self-citationFisetin protects against hepatosteatosis in mice by inhibiting miR-378
Jeon, T., Park, J. W., Ahn, J., Jung, C. H., & Ha, T. Y. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300071 · Cited by 47
Zhang, T., Zhao, X., Steer, C. J., Yan, G., & Song, G. (2018) · Metabolism · doi:10.1016/j.metabol.2018.03.023 · Cited by 46
Self-citationThe Receptor Interacting Protein Kinases in the Liver
Dara, L. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1629924 · Cited by 43
Jayandharan, G. R., Li, Z., Sack, B. K., Rivers, A. E., Li, M., Li, B., Herzog, R. W., & Srivastava, A. (2009) · Human Gene Therapy · doi:10.1089/hum.2009.100 · Cited by 38
Self-citationIssa, D., & Alkhouri, N. (2017) · Hepatobiliary surgery and nutrition · doi:10.21037/hbsn.2017.07.07 · Cited by 19
Ali, M., Laçin, Ş., Abdel‐Wahab, R., Uemura, M. I., Hassan, M. M., Rashid, A., Duda, D. G., & Kaseb, A. O. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s111681 · Cited by 10
MicroRNAs as Mediators in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Steatohepatitis
Becker, P., Niesler, B., Tschopp, O., Berr, F., Canbay, A. E., Dandekar, T., Müllhaupt, B., Schmitt, J., & Geier, A. (2014) · Zeitschrift für Gastroenterologie · doi:10.1055/s-0033-1360871 · Cited by 5
Research works printed but not linked: 1
- Foog, 2017, Managing HCC in NAFLD. Curr Hepatol, Rep, 16, 374
Cited by
Sorted by citations
The sirtuin family in health and disease
Wu, Q., Zhang, T., Chen, H., Yu, X., Lv, J.-L., Liu, Y., Liu, Y., Zheng, G., Zhao, J.-Q., Wei, Y., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01257-8 · Cited by 928
Self-citationMicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases
Wang, X., He, Y., Mackowiak, B., & Gao, B. (2020) · Gut · doi:10.1136/gutjnl-2020-322526 · Cited by 491
Self-citationEpigenetic regulation in metabolic diseases: mechanisms and advances in clinical study
Wu, Y., Lin, Z., Li, C., Lin, X. J., Shan, S., Guo, B., Zheng, M.-H., Li, F., Yuan, L., & Li, Z. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01333-7 · Cited by 549
Self-citationNAFLD: Mechanisms, Treatments, and Biomarkers
Nassir, F. (2022) · Biomolecules · doi:10.3390/biom12060824 · Cited by 452
Relevance of SIRT1-NF-κB Axis as Therapeutic Target to Ameliorate Inflammation in Liver Disease
de Gregorio, E., Colell, A., Morales, A., & Marí, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113858 · Cited by 204
Metadata
- Authors
- Zhang, T., Hu, J., Wang, X., Zhao, X., Li, Z., Niu, J., Steer, C. J., Zheng, G., & Song, G.
- Affiliations
- University of Minnesota (US)
- Hubei University of Chinese Medicine (CN)
- Jilin University (CN)
- Shanxi University (CN)
- Corresponding author
- Zheng, Guohua
- Song, Guisheng
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 70
- Issue
- 1
- Pages
- 87-96
- ISSN
- 0168-8278 (ISSN-L)
- PMC
- PMC6554744
- OpenAlex
- W2890391525
- Cited by
- 196
- References
- 43
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 34 · 2023: 23 · 2022: 37 · 2021: 43 · 2020: 14 · 2019: 7
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 DK102601)
- American Cancer Society (ISG-16-210-01-RMC)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- miR-378, nonalcoholic steatohepatitis, liver inflammation, liver fibrosis, NF-κB signaling, TNF signaling, PRKAG2, AMPK, SIRT1, obesity, high-fat diet, microRNA, therapeutic target, hepatocellular carcinoma risk, liver-specific gene expression
- MeSH terms
- Animals, Biopsy, Disease Models, Animal, Gene Expression Regulation, Hepatitis, Humans, Immunohistochemistry, Liver, Liver Cirrhosis, Male, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Immunoblotting, Signal Transduction, NF-kappa B, Disease Progression, MicroRNAs, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
