ArticlePloS one2013
Inhibition of protein kinase C delta attenuates allergic airway inflammation through suppression of PI3K/Akt/mTOR/HIF-1 alpha/VEGF pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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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.
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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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Roles of PI3K pan-inhibitors and PI3K-δ inhibitors in allergic lung inflammation: a systematic review and meta-analysis.Scientific reports · 2020Pooled it
- Glycyrrhizin preparations in liver diseases: a narrative review of mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- The dual role of mTOR signaling in lung development and adult lung diseases.Cell & bioscience · 2025Review
- Triolein alleviates ischemic stroke brain injury by regulating autophagy and inflammation through the AKT/mTOR signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- The decoy oligodeoxynucleotide against HIF-1α and STAT5 ameliorates atopic dermatitis-like mouse model.Molecular therapy. Nucleic acids · 2023Article
- Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method.Scientific reports · 2023Article
- Black Ginseng Extract Exerts Potentially Anti-Asthmatic Activity by Inhibiting the Protein Kinase Cθ-Mediated IL-4/STAT6 Signaling Pathway.International journal of molecular sciences · 2023Article
- Pathogenesis of allergic diseases and implications for therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Expression of HIF-1α in pediatric asthmatic patients.Multidisciplinary respiratory medicine · 2023Article
- The Interaction of Food Allergy and Diabetes: Food Allergy Effects on Diabetic Mice by Intestinal Barrier Destruction and Glucagon-like Peptide 1 Reduction in Jejunum.Foods (Basel, Switzerland) · 2022Article
- The metabolomics of a protein kinase C delta (PKCδ) knock-out mouse model.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Development of a Novel Targeted Metabolomic LC-QqQ-MS Method in Allergic Inflammation.Metabolites · 2022Article
- Compound K ameliorates airway inflammation and mucus secretion through the regulation of PKC signaling in vitro and in vivo.Journal of ginseng research · 2022Article
- The role of Wnt/mTOR signaling in spinal cord injury.Journal of clinical orthopaedics and trauma · 2022Review
- The CCCH-Type Zinc Finger Antiviral Protein Relieves Immunosuppression of T Cells Induced by Avian Leukosis Virus Subgroup J via the NLP-PKC-δ-NFAT Pathway.Journal of virology · 2022Article
- Exploring the Mechanism of the miRNA-145/Paxillin Axis in Cell Metabolism During VEGF-A-Induced Corneal Angiogenesis.Investigative ophthalmology & visual science · 2021Article
- Trigonelline, An Alkaloid FromFrontiers in pharmacology · 2021Article
- Comparison of COVID-19 and Lung CancerFrontiers in oncology · 2021Review
- Shuxuening injection, derived fromPharmaceutical biology · 2020Article
- In vitro anti-inflammatory effects of curcumin on mast cell-mediated allergic responses via inhibiting FcεRI protein expression and protein kinase C delta translocation.Cytotechnology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor (VEGF) is supposed to contribute to the pathogenesis of allergic airway disease. VEGF expression is regulated by a variety of stimuli such as nitric oxide, growth factors, and hypoxia-inducible factor-1 alpha (HIF-1α). Recently, inhibition of the mammalian target of rapamycin (mTOR) has been shown to alleviate cardinal asthmatic features, including airway hyperresponsiveness, eosinophilic inflammation, and increased vascular permeability in asthma models. Based on these observations, we have investigated whether mTOR is associated with HIF-1α-mediated VEGF expression in allergic asthma. In studies with the mTOR inhibitor rapamycin, we have elucidated the stimulatory role of a mTOR-HIF-1α-VEGF axis in allergic response. Next, the mechanisms by which mTOR is activated to modulate this response have been evaluated. mTOR is known to be regulated by phosphoinositide 3-kinase (PI3K)/Akt or protein kinase C-delta (PKC δ) in various cell types. Consistent with these, our results have revealed that suppression of PKC δ by rottlerin leads to the inhibition of PI3K/Akt activity and the subsequent blockade of a mTOR-HIF-1α-VEGF module, thereby attenuating typical asthmatic attack in a murine model. Thus, the present data indicate that PKC δ is necessary for the modulation of the PI3K/Akt/mTOR signaling cascade, resulting in a tight regulation of HIF-1α activity and VEGF expression. In conclusion, PKC δ may represent a valuable target for innovative therapeutic treatment of allergic airway disease.
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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.