ArticlePloS one2015
PI3K-AKT Signaling via Nrf2 Protects against Hyperoxia-Induced Acute Lung Injury, but Promotes Inflammation Post-Injury Independent of Nrf2 in Mice.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- A novel curcumin analog sAc15 alleviates LPS-induced acute lung injury by activating the PI3K/AKT/Nrf2 pathway in pulmonary epithelial cells.Redox report : communications in free radical research · 2026Article
- 6β-Acetoxysandaracopimaradien-1α,9α-diol Attenuates LPS-Induced Acute Lung Injury: Association with Alterations in Src, MAPK, and Akt/GSK-3β Signalling.International journal of molecular sciences · 2026Article
- Advances in research on hyperoxia-induced acute lung injury: from pathogenesis to therapy.Frontiers in cell and developmental biology · 2026Review
- Vitamin K3 Analog Phthiocol Protects Against High Phosphate-Induced Vascular Calcification in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2025Article
- Harpagide Confers Protection Against Acute Lung Injury Through Multi-Omics Dissection of Immune-Microenvironmental Crosstalk and Convergent Therapeutic Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Flavonoids from Polygonum hydropiper L. regulate PCV2-induced oxidative stress of RAW264.7 cells via Pi3k/AKT and Nrf2/HO-1 signaling pathways.Scientific reports · 2025Article
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- The therapeutic potential of RNA m(6)A in lung cancer.Cell communication and signaling : CCS · 2024Review
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- Recombinant CXCL17 Treatment Alleviates Hyperoxia-Induced Lung Apoptosis and Inflammation In Vivo and Vitro by Activating the AKT Pathway: A Possible Therapeutic Approach for Bronchopulmonary Dysplasia.Molecular biotechnology · 2024Article
- Resolving candidate genes of duck ovarian tissue transplantation via RNA-Seq and expression network analyses.Poultry science · 2024Article
- Vitamin C Alleviates the Negative Effects of Heat Stress on Reproductive Processes by Regulating Amino Acid Metabolism in Granulosa Cells.Antioxidants (Basel, Switzerland) · 2024Article
- SLAB51 Multi-Strain Probiotic Formula Increases Oxygenation in Oxygen-Treated Preterm Infants.Nutrients · 2023Article
- Review
- Molecular Mechanisms of High-Altitude Acclimatization.International journal of molecular sciences · 2023Review
- Normal and Pathological NRF2 Signalling in the Central Nervous System.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- Article
- Major Nutritional Metabolic Alterations Influencing the Reproductive System of Postpartum Dairy Cows.Metabolites · 2022Review
- Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K/AKT/Nrf2 pathway.Pharmaceutical biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Lung epithelial and endothelial cell death accompanied by inflammation contributes to hyperoxia-induced acute lung injury (ALI). Impaired resolution of ALI can promote and/or perpetuate lung pathogenesis, including fibrosis. Previously, we have shown that the transcription factor Nrf2 induces cytoprotective gene expression and confers protection against hyperoxic lung injury, and that Nrf2-mediated signaling is also crucial for the restoration of lung homeostasis post-injury. Although we have reported that PI3K/AKT signaling is required for Nrf2 activation in lung epithelial cells, significance of the PI3K/AKT-Nrf2 crosstalk during hyperoxic lung injury and repair remains unclear. Thus, we evaluated this aspect using Nrf2 knockout (Nrf2(-/-)) and wild-type (Nrf2(+/+)) mouse models. Here, we show that pharmacologic inhibition of PI3K/AKT signaling increased lung inflammation and alveolar permeability in Nrf2(+/+) mice, accompanied by decreased expression of Nrf2-target genes such as Nqo1 and Hmox1. PI3K/AKT inhibition dampened hyperoxia-stimulated Nqo1 and Hmox1 expression in lung epithelial cells and alveolar macrophages. Contrasting with its protective effects, PI3K/AKT inhibition suppressed lung inflammation in Nrf2(+/+) mice during post-injury. In Nrf2(-/-) mice exposed to room-air, PI3K/AKT inhibition caused lung injury and inflammation, but it did not exaggerate hyperoxia-induced ALI. During post-injury, PI3K/AKT inhibition did not augment, but rather attenuated, lung inflammation in Nrf2(-/-) mice. These results suggest that PI3K/AKT-Nrf2 signaling is required to dampen hyperoxia-induced lung injury and inflammation. Paradoxically, the PI3K/AKT pathway promotes lung inflammation, independent of Nrf2, during post-injury.
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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 OpenQuestion graph.