ArticleCells2019
Akt1 and Akt2 Isoforms Play Distinct Roles in Regulating the Development of Inflammation and Fibrosis Associated with Alcoholic Liver Disease.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Treatment of liver fibrosis in hepatolenticular degeneration with traditional Chinese medicine: systematic review of meta-analysis, network pharmacology and molecular dynamics simulation.Frontiers in medicine · 2023Pooled it
- PTEN-AKT2 regulates mixed lineage liver cancer development and sensitizes cancer cells to TGFβ treatment.Oncogene · 2026Article
- Complex interactions between miR-107 and PTEN gene expression, more specifically in viral and NASH cirrhosis.Biochemistry and biophysics reports · 2026Article
- PTEN-AKT2 Regulates Mixed Lineage Liver Cancer Development and Sensitizes Cancer Cells to TGFβ Treatment.Research square · 2026Article
- Discovery of an AKT1-targeting compound from a traditional herbal formula for alcoholic liver disease via integrative computational and experimental approaches.Chinese medicine · 2025Article
- Integrating Strategy of Network Pharmacology, Molecular Dynamics Simulation, and Experimental Verification to Investigate the Potential Mechanism ofFoods (Basel, Switzerland) · 2025Article
- LncRNA UCA1 regulates immune micro-environment in cisplatin-induced AKI by miRNA-4498/AKT3 pathway.PloS one · 2025Article
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Metabolomic Profiling and Network Toxicology: Mechanistic Insights into Effect of Gossypol Acetate Isomers in Uterine Fibroids and Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Article
- Structural Characterization and Anti-Inflammatory Activity of Polysaccharides fromFoods (Basel, Switzerland) · 2023Article
- Study on the Alleviating Effect and Potential Mechanism of Ethanolic Extract ofInternational journal of molecular sciences · 2023Article
- System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.International journal of molecular sciences · 2023Article
- Exploring the effect of Yinzhihuang granules on alcoholic liver disease based on pharmacodynamics, network pharmacology and molecular docking.Chinese medicine · 2023Article
- Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation.Frontiers in immunology · 2023Article
- Network Pharmacology and Molecular Docking Reveal the Mechanism ofDrug design, development and therapy · 2023Article
- Network analysis of liver cancer: a system biology approach.Gastroenterology and hepatology from bed to bench · 2023Article
- Article
- Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study.Nutrients · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Akt kinase isoforms (Akt1, Akt2, and Akt3) have generally been thought to play overlapping roles in phosphoinositide 3-kinase (PI3K)-mediated-signaling. However, recent studies have suggested that they display isoform-specific roles in muscle and fat. To determine whether such isoform-specificity is observed with respect to alcoholic liver disease (ALD) progression, we examined the role of Akt1, Akt2, and Akt3 in hepatic inflammation, and pro-fibrogenic proliferation and migration using Kupffer cells, hepatic stellate cells (HSC), and hepatocytes in an ethanol and lipopolysaccharide (LPS)-induced two-hit model in vitro and in vivo. We determined that siRNA-directed silencing of Akt2, but not Akt1, significantly suppressed cell inflammatory markers in HSC and Kupffer cells. Although both Akt1 and Akt2 inhibited cell proliferation in HSC, only Akt2 inhibited cell migration. Both Akt1 and Akt2, but not Akt3, inhibited fibrogenesis in hepatocytes and HSC. In addition, our in vivo results show that administration of chronic ethanol, binge ethanol and LPS (EBL) in wild-type C57BL/6 mice activated all three Akt isoforms with concomitant increases in activated forms of phosphoinositide dependent kinase-1 (PDK1), mammalian target-of-rapamycin complex 2 (mTORC2), and PI3K, resulting in upregulation in expression of inflammatory, proliferative, and fibrogenic genes. Moreover, pharmacological blocking of Akt2, but not Akt1, inhibited EBL-induced inflammation while blocking of both Akt1 and Akt2 inhibited pro-fibrogenic marker expression and progression of fibrosis. Our findings indicate that Akt isoforms play unique roles in inflammation, cell proliferation, migration, and fibrogenesis during EBL-induced liver injury. Thus, close attention must be paid when targeting all Akt isoforms as a therapeutic intervention.
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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.