ArticlePloS one2021
Tenofovir disoproxil fumarate directly ameliorates liver fibrosis by inducing hepatic stellate cell apoptosis via downregulation of PI3K/Akt/mTOR signaling pathway.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Host-parasite cross-species regulation by Schistosoma japonicum EV-miRNA sja-miR-2a-3p limits hepatic fibrosis via BCL2 suppression in hepatic stellate cells.Veterinary research · 2026Article
- Multi-Omics Integration Uncovers That Tenofovir Disoproxil Fumarate Is Linked to Hepatic Metabolic Reprogramming Independent of Viral Infection.Life (Basel, Switzerland) · 2026Article
- <p>Beyond hepatic stellate cell heterogeneity: Resolving fibrosis, restoring regeneration (Review)</p>.International journal of molecular medicine · 2026Review
- Xanthine oxidase inhibition by medicinal plants mitigates tenofovir-induced nephrotoxicity: a comprehensive computational and experimental study.Frontiers in pharmacology · 2026Article
- Angiotensin-Converting Enzyme Inhibitors to Prevent Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Scientific Speculation or an Opportunity to Improve Real Clinical Practice?International journal of molecular sciences · 2025Review
- Besifovir dipivoxil maleate versus other antivirals in reducing hepatocellular carcinoma in chronic hepatitis B.Scientific reports · 2025Article
- Tenofovir attenuates cytokine storm and bronchiolar damage in a mouse model of bleomycin-induced acute lung injury.Scientific reports · 2025Article
- ADSCs attenuate Liver fibrosis via inducing HSC senescence: validation in dual-etiology models.PLoS neglected tropical diseases · 2025Article
- Fibrosis and Hepatocarcinogenesis: Role of Gene-Environment Interactions in Liver Disease Progression.International journal of molecular sciences · 2024Review
- Long-Term HBsAg Titer Kinetics with Entecavir/Tenofovir: Implications for Predicting Functional Cure and Low Levels.Diagnostics (Basel, Switzerland) · 2024Article
- Nrf2/HO-1, NF-κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats.Journal of cellular and molecular medicine · 2024Article
- Phomopsterone B Alleviates Liver Fibrosis through mTOR-Mediated Autophagy and Apoptosis Pathway.Molecules (Basel, Switzerland) · 2024Article
- Molecular Biological Mechanisms of Action of Chrysophanol in Hepatic Stellate Cells Activated by Hepatic B Virus X Based on Network Pharmacology.Intervirology · 2024Article
- Signaling pathways that activate hepatic stellate cells during liver fibrosis.Frontiers in medicine · 2024Review
- [Quercetin induces hepatic stellate cell apoptosis by inhibiting the PI3K/Akt signaling pathwayNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- [Impact of nucleosides analogues and nucleotide analogues on the outcomes related to chronic hepatitis B based on non-antiviral effects].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Review
- Improved on-treatment fibrosis-4 during antiviral therapy and lower hepatocellular carcinoma risk in cirrhotic patients with hepatitis B.Scientific reports · 2023Article
- Liver Fibrosis Resolution: From Molecular Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2023Review
- Review
- TACE versus TACE + entecavir versus TACE + tenofovir in the treatment of HBV associated hepatocellular carcinoma.BMC cancer · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAntifibrotic agent for the treatment of liver fibrosis has not been developed so far. Long term treatment of chronic hepatitis B patients with antiviral drugs tenofovir disoproxil fumarate (TDF) and entecavir (ETV) results in the regression of liver fibrosis, but the underlying mechanism has not been clarified. Therefore, we aimed to investigate the direct impact of TDF and ETV on liver fibrosis.
methodsActivated hepatic stellate cell (HSC) cell lines were used to evaluate the effects of TDF and ETV. After treatment with each antiviral agent, cell viability, morphology, apoptotic features, autophagy and antifibrosis signalling pathways were examined. Then, collagen deposition, fibrosis markers and activated HSCs were measured in liver tissues of the liver fibrosis model mice.
resultsAfter TDF treatment, the viabilities of LX2 and HSC-T6 cells were decreased, and the cells exhibited apoptotic features, but ETV did not induce these effects. Cleavage of PARP and Caspase-3 and the inhibition of the antiapoptotic gene Bcl-xl indicated activated HSC apoptosis following TDF treatment. TDF simultaneously increased autophagy, which also regulated apoptosis through crosstalk. TDF inactivated the PI3K/Akt/mTOR signalling pathway, which was associated with the activation of both apoptosis and autophagy. In the liver fibrosis mouse model, the fibrotic area and activated HSC markers were decreased by TDF but not ETV treatment. Additionally, apoptotic cells were concentrated in the periportal fibrotic area after TDF treatment, which indicated the specific antifibrotic effect of TDF.
conclusionsTDF directly ameliorates liver fibrosis by downregulating the PI3K/Akt/mTOR signalling pathway, which results in the apoptosis of activated HSCs. The antifibrotic effects of TDF indicate that it may be a therapeutic agent for the treatment of liver 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 Socratic graph.