Trial reportThe Journal of biological chemistry2013
The autoregulatory feedback loop of microRNA-21/programmed cell death protein 4/activation protein-1 (MiR-21/PDCD4/AP-1) as a driving force for hepatic fibrosis development.
Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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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.
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.
Who cites it
76 citing papers in PubMed, 127 citations in OpenAlex.
- MicroRNA Control of Hepatocyte-Stromal Crosstalk in the Early Premalignant Microenvironment of HBV-Associated HCC.International journal of molecular sciences · 2026Review
- Non-coding RNA networks in metabolic dysfunction-associated steatotic liver disease: Mechanisms and therapeutic perspectives.Liver research (Beijing, China) · 2026Review
- MicroRNA Regulation in Kidney Interstitial Fibrosis.Epigenomes · 2026Review
- Extracellular Vesicles in Liver Disease: Redefining Diagnostic and Therapeutic Strategies.International journal of stem cells · 2026Review
- Mechanistic insights into post-translational modifications in hepatic fibrosis: pathogenic roles and therapeutic potentials.Journal of translational medicine · 2025Review
- Evaluation of Five Plasma miRNAs as Biomarkers for Minimally Invasive Staging of Liver Fibrosis in β-Thalassaemia Patients.International journal of molecular sciences · 2025Article
- Hepatocyte delivery of miR-34b/c reduces hepatic stellate cell activation and improves liver fibrosis.Molecular therapy. Nucleic acids · 2025Article
- Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis by inhibiting hepatocyte ferroptosis and macrophage polarization via the miR-455-3p/PLAU axis.Stem cell research & therapy · 2025Article
- Expression Analysis of Circulating miR-21, miR-34a and miR-122 and Redox Status Markers in Metabolic Dysfunction-Associated Steatotic Liver Disease Patients with and Without Type 2 Diabetes.International journal of molecular sciences · 2025Article
- MicroRNA-21 Promotes the Viability, Proliferation and Milk Fat Synthesis of Ovine Mammary Epithelial Cells by TargetingInternational journal of molecular sciences · 2025Article
- The interactive role of microRNA and other non-coding RNA in hepatitis B (HBV) associated fibrogenesis.Functional & integrative genomics · 2025Review
- Lnc NBAT1 Inhibits the Proliferation and Migration of Liver Cancer Cells Through the miR-21/PDCD4/AP-1 Signaling Axis.Applied biochemistry and biotechnology · 2025Article
- Quantitative Proteomic Study Reveals Amygdalin Alleviates Liver Fibrosis Through Inhibiting mTOR/PDCD4/JNK Pathway in Hepatic Stellate Cells.Drug design, development and therapy · 2025Article
- Review
- Investigates the Role of PANoptosis in Idiopathic Pulmonary Fibrosis and Potential Therapeutic Targets.Journal of inflammation research · 2024Article
- Role of noncoding RNAs in liver fibrosis.World journal of gastroenterology · 2023Review
- The role of microRNAs in the modulation of cancer-associated fibroblasts activity during pancreatic cancer pathogenesis.Journal of physiology and biochemistry · 2023Review
- miR-21 promotes the fibrotic properties in oral mucosa through targeting PDCD4.Journal of dental sciences · 2022Article
- Osteoblast Derived Exosomes Alleviate Radiation- Induced Hematopoietic Injury.Frontiers in bioengineering and biotechnology · 2022Article
- Delivery of microRNA-21-sponge and pre-microRNA-122 by MS2 virus-like particles to therapeutically target hepatocellular carcinoma cells.Experimental biology and medicine (Maywood, N.J.) · 2021Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sustained activation of hepatic stellate cells (HSCs) leads to hepatic fibrosis, which is characterized by excessive collagen production, and for which there is no available drug clinically. Despite tremendous progress, the cellular activities underlying HSC activation, especially the driving force in the perpetuation stage, are only partially understood. Recently, microRNA-21 (miR-21) has been found to be prevalently up-regulated during fibrogenesis in different tissues, although its detailed role needs to be further elucidated. In the present study, miR-21 expression was examined in human cirrhotic liver samples and in murine fibrotic livers induced by thioacetamide or carbon tetrachloride. A dramatic miR-21 increase was noted in activated HSCs. We further found that miR-21 maintained itself at constant high levels by using a microRNA-21/programmed cell death protein 4/activation protein-1 (miR-21/PDCD4/AP-1) feedback loop. Disrupting this loop with miR-21 antagomir or AP-1 inhibitors significantly suppressed fibrogenic activities in HSCs and ameliorated liver fibrosis. In contrast, reinforcing this loop with small interfering RNA (siRNA) against PDCD4 promoted fibrogenesis in HSCs. Further analysis indicated that the up-regulated miR-21 promoted the central transforming growth factor-β (TGF-β) signaling pathway underlying HSC activation. In summary, we suggest that the miR-21/PDCD4/AP-1 autoregulatory loop is one of the main driving forces for hepatic fibrosis progression. Targeting this aberrantly activated feedback loop may provide a new therapeutic strategy and facilitate drug discovery against hepatic fibrosis.
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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.