ArticleBritish journal of pharmacology2015
The Akt inhibitor, triciribine, ameliorates chronic hypoxia-induced vascular pruning and TGFβ-induced pulmonary fibrosis.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Direct pharmacological targeting of RAC1 by chlorogenic acid: A novel therapeutic approach for mesangial proliferative glomerulonephritis.Acta pharmaceutica Sinica. B · 2026Article
- Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway.The world journal of men's health · 2025Article
- Astragaloside promotes the secretion of MSC-derived exosomal miR-146a-5p by regulating TRAF6/NF-κB pathway to attenuate inflammation in high glucose-impaired endothelial cells.In vitro cellular & developmental biology. Animal · 2025Article
- PI3K/Akt in IPF: untangling fibrosis and charting therapies.Frontiers in immunology · 2025Review
- DsbA-L activates TGF-β1/SMAD3 signaling and M2 macrophage polarization by stimulating AKT1 and NLRP3 to promote pulmonary fibrosis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Comparison of Biomarkers Playing a Role in Pterygium Development in Pterygium and Recurrent Pterygium Tissues.Diagnostics (Basel, Switzerland) · 2024Article
- CD47 and thrombospondin-1 contribute to immune evasion byProceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Quercetin: A Flavonoid with Potential for Treating Acute Lung Injury.Drug design, development and therapy · 2024Review
- A multi-arm, parallel, preclinical study investigating the potential benefits of acetazolamide, candesartan, and triciribine in combination with fluconazole for the treatment of cryptococcal meningoencephalitis.European journal of pharmacology · 2023Article
- Is there a role for specialized pro-resolving mediators in pulmonary fibrosis?Pharmacology & therapeutics · 2023Review
- Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative retinopathy.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Akt-independent effects of triciribine on ACE2 expression in human lung epithelial cells: Potential benefits in restricting SARS-CoV2 infection.Journal of cellular physiology · 2021Article
- Distinct effects of pharmacological inhibition of stromelysin1 on endothelial-to-mesenchymal transition and myofibroblast differentiation.Journal of cellular physiology · 2021Article
- Superior mechanical recovery in male and female MRL/MpJ tendons is associated with a unique genetic profile.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Article
- Cisatracurium attenuates LPS-induced modulation of MMP3 and junctional protein expression in human microvascular endothelial cells.Bioscience trends · 2021Article
- Article
- Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome.Mediators of inflammation · 2021Article
- Biochanin-A ameliorates pulmonary fibrosis by suppressing the TGF-β mediated EMT, myofibroblasts differentiation and collagen deposition in in vitro and in vivo systems.Phytomedicine : international journal of phytotherapy and phytopharmacology · 2020Article
- Exendin-4 inhibits atrial arrhythmogenesis in a model of myocardial infarction-induced heart failure via the GLP-1 receptor signaling pathway.Experimental and therapeutic medicine · 2020Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
background and purposeInterstitial lung disease accounts for a group of chronic and progressive disorders associated with severe pulmonary vascular remodelling, peripheral vascular rarefaction and fibrosis, thus limiting lung function. We have previously shown that Akt is necessary for myofibroblast differentiation, a critical event in organ fibrosis. However, the contributory role of the Akt-mTOR pathway in interstitial lung disease and the therapeutic benefits of targeting Akt and mTOR remain unclear. EXPERIMENTAL APPROACH: We investigated the role of the Akt-mTOR pathway and its downstream molecular mechanisms in chronic hypoxia- and TGFβ-induced pulmonary vascular pruning and fibrosis in mice. We also determined the therapeutic benefits of the Akt inhibitor triciribine and the mTOR inhibitor rapamycin for the treatment of pulmonary fibrosis in mice. KEY
resultsAkt1(-) (/) (-) mice were protected from chronic hypoxia-induced peripheral vascular pruning. In contrast, hyperactivation of Akt1 induced focal fibrosis similar to TGFβ-induced fibrosis. Pharmacological inhibition of Akt, but not the Akt substrate mTOR, inhibited hypoxia- and TGFβ-induced pulmonary vascular rarefaction and fibrosis. Mechanistically, we found that Akt1 modulates pulmonary remodelling via regulation of thrombospondin1 (TSP1) expression. Hypoxic Akt1(-) (/) (-) mice lungs expressed less TSP1. Moreover, TSP1(-) (/) (-) mice were resistant to adMyrAkt1-induced pulmonary fibrosis. CONCLUSIONS AND IMPLICATIONS: Our study identified Akt1 as a novel target for the treatment of interstitial lung disease and provides preclinical data on the potential benefits of the Akt inhibitor triciribine for the treatment of interstitial lung disease.
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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.