ArticleIntensive care medicine2010
Pulmonary-derived phosphoinositide 3-kinase gamma (PI3Kγ) contributes to ventilator-induced lung injury and edema.
Article in Intensive care medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Beyond the mutations: spatiotemporal regulation of CFTR by cAMP and calcium signaling in epithelial physiology and cystic fibrosis.Cellular & molecular biology letters · 2025Review
- Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model.International journal of molecular sciences · 2025Article
- Human liver stem cells and derived extracellular vesicles protect from sepsis-induced acute lung injury and restore bone marrow myelopoiesis in a murine model of sepsis.Intensive care medicine experimental · 2024Article
- A PI3Kγ mimetic peptide triggers CFTR gating, bronchodilation, and reduced inflammation in obstructive airway diseases.Science translational medicine · 2022Article
- Identifying Active Compounds and Mechanisms ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Ventilator-induced lung-injury in mouse models: Is there a trap?Laboratory animal research · 2021Review
- Review
- A pathophysiological role of PDE3 in allergic airway inflammation.JCI insight · 2018Article
- Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury.Oxidative medicine and cellular longevity · 2017Article
- Saikosaponin-d attenuates ventilator-induced lung injury in rats.International journal of clinical and experimental medicine · 2015Article
- Mitochondrial Targeted Endonuclease III DNA Repair Enzyme Protects against Ventilator Induced Lung Injury in Mice.Pharmaceuticals (Basel, Switzerland) · 2014Article
- Mitochondrial-targeted DNA repair enzyme 8-oxoguanine DNA glycosylase 1 protects against ventilator-induced lung injury in intact mice.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Using the one-lung method to link p38 to pro-inflammatory gene expression during overventilation in C57BL/6 and BALB/c mice.PloS one · 2012Article
- Year in review in Intensive Care Medicine 2010: I. Acute renal failure, outcome, risk assessment and ICU performance, sepsis, neuro intensive care and experimentals.Intensive care medicine · 2011Article
- Animal models of airway diseases.Sub-cellular biochemistry · 2011Review
- Experimental trauma models: an update.Journal of biomedicine & biotechnology · 2011Review
- Small interfering RNA (siRNA): a hope for the loss-of-function studies in anesthesiology?Korean journal of anesthesiology · 2010Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVentilator-induced lung injury (VILI) occurs in part by increased vascular permeability and impaired alveolar fluid clearance. Phosphoinositide 3-kinase gamma (PI3Kγ) is activated by mechanical stress, induces nitric oxide (NO) production, and participates in cyclic adenosine monophosphate (cAMP) hydrolysis, each of which contributes to alveolar edema. We hypothesized that lungs lacking PI3Kγ or treated with PI3Kγ inhibitors would be protected from ventilation-induced alveolar edema and lung injury.
methodsUsing an isolated and perfused lung model, wild-type (WT) and PI3Kγ-knockout (KO) mice underwent negative-pressure cycled ventilation at either -25 cmH₂O and 0 cmH₂O positive end-expiratory pressure (PEEP) (HIGH STRESS) or -10 cmH₂O and -3 cmH₂O PEEP (LOW STRESS).
resultsCompared with WT, PI3Kγ-knockout mice lungs were partially protected from VILI-induced derangement of respiratory mechanics (lung elastance) and edema formation [bronchoalveolar lavage (BAL) protein concentration, wet/dry ratio, and lung histology]. In PI3Kγ-knockout mice, VILI induced significantly less phosphorylation of protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), production of nitrate and nitrotyrosine, as well as hydrolysis of cAMP, compared with wild-type animals. PI3Kγ wild-type lungs treated with AS605240, an inhibitor of PI3Kγ kinase activity, in combination with enoximone, an inhibitor of phosphodiesterase-3 (PDE3)-induced cAMP hydrolysis, were protected from VILI at levels comparable to knockout lungs.
conclusionsPhosphoinositide 3-kinase gamma in resident lung cells mediates part of the alveolar edema induced by high-stress ventilation. This injury is mediated via altered Akt, eNOS, NO, and/or cAMP signaling. Anti-PI3Kγ therapy aimed at resident lung cells represents a potential pharmacologic target to mitigate VILI.
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