ArticlePloS one2019
Gas6/Axl signaling attenuates alveolar inflammation in ischemia-reperfusion-induced acute lung injury by up-regulating SOCS3-mediated pathway.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Prenatal Naproxen Reprograms Histopathological and Molecular Facets of the Sex-Based Lung Injury in Adult Offspring of Preeclamptic Rats.International journal of molecular sciences · 2026Article
- PROS1/AXL signaling protects mice from lethal influenza infection by inducing M2 macrophage polarization.Acta biochimica et biophysica Sinica · 2025Article
- Recent advances in TAM mechanisms in lung diseases.Journal of translational medicine · 2025Review
- Pleiotropic role of GAS6 in cardioprotection against ischemia-reperfusion injury.Journal of advanced research · 2025Article
- Activated AXL Ameliorates Alcohol-associated Steatotic Liver Ischemia-Reperfusion Injury by Inhibiting ER stress and Mitochondria-associated Apoptosis.International journal of biological sciences · 2025Article
- Fetal hypoplastic lungs have multilineage inflammation that is reversed by amniotic fluid stem cell extracellular vesicle treatment.Science advances · 2024Article
- Could Gas6/TAM Axis Provide Valuable Insights into the Pathogenesis of Systemic Sclerosis?Current issues in molecular biology · 2024Review
- Identification of SOCS3 and PTGS2 as new biomarkers for the diagnosis of gout by cross-species comprehensive analysis.Heliyon · 2024Article
- Administration of Gas6 attenuates lung fibrosis via inhibition of the epithelial-mesenchymal transition and fibroblast activation.Cell biology and toxicology · 2024Article
- Differential regulation of lung homeostasis and silicosis by the TAM receptors MerTk and Axl.Frontiers in immunology · 2024Article
- Modulation of recovery from neonatal hyperoxic lung injury by sex as a biological variable.Redox biology · 2023Article
- Gas6/Axl Axis Activation Dampens the Inflammatory Response in Osteoarthritic Fibroblast-like Synoviocytes and Synovial Explants.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Exome-Wide Association Study Reveals Host Genetic Variants Likely Associated with the Severity of COVID-19 in Patients of European Ancestry.Life (Basel, Switzerland) · 2022Article
- The Akt-mTORC1 pathway mediates Axl receptor tyrosine kinase-induced mesangial cell proliferation.Journal of leukocyte biology · 2022Article
- The First Evaluation of Serum Levels of MGP, Gas6 and EGFR after First Dose of Chemotherapy in Lung Cancer.Biology · 2022Article
- Regulatory Networks, Management Approaches, and Emerging Treatments of Nonalcoholic Fatty Liver Disease.Canadian journal of gastroenterology & hepatology · 2022Review
- Gas6/TAM Signalling Negatively Regulates Inflammatory Induction of GM-CSF in Mouse Brain Microglia.Cells · 2021Article
- Vitamin K Effects on Gas6 and Soluble Axl Receptors in Intensive Care Patients: An Observational Screening Study.Nutrients · 2021Observational
- Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury.Biomedicines · 2021Article
- Deficiency of Axl aggravates pulmonary arterial hypertension via BMPR2.Communications biology · 2021Article
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7 authors at 3 institutions in 1 country.
Funding
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Abstract
backgroundAxl is a cell surface receptor tyrosine kinase, and activation of the Axl attenuates inflammation induced by various stimuli. Growth arrest-specific 6 (Gas6) has high affinity for Axl receptor. The role of Gas6/Axl signaling in ischemia-reperfusion-induced acute lung injury (IR-ALI) has not been explored previously. We hypothesized that Gas6/Axl signaling regulates IR-induced alveolar inflammation via a pathway mediated by suppressor of cytokine signaling 3 (SOCS3).
methodsIR-ALI was induced by producing 30 min of ischemia followed by 90 min of reperfusion in situ in an isolated and perfused rat lung model. The rats were randomly allotted to a control group and IR groups, which were treated with three different doses of Gas6. Mouse alveolar epithelium MLE-12 cells were cultured in control and hypoxia-reoxygenation (HR) conditions with or without Gas6 and Axl inhibitor R428 pretreatment.
resultsWe found that Gas6 attenuated IR-induced lung edema, the production of proinflammatory cytokines in perfusates, and the severity of ALI ex vivo. IR down-regulated SOCS3 expression and up-regulated NF-κB, and Gas6 restored this process. In the model of MLE-12 cells with HR, Gas6 suppressed the activation of TRAF6 and NF-κB by up-regulating SOCS3. Axl expression of alveolar epithelium was suppressed in IR-ALI but Gas6 restored phosphorylation of Axl. The anti-inflammatory effect of Gas6 was antagonized by R428, which highlighted that phosphorylation of Axl mediated the protective role of Gas6 in IR-ALI.
conclusionsGas6 up-regulates phosphorylation of Axl on alveolar epithelium in IR-ALI. The Gas6/Axl signaling activates the SOCS3-mediated pathway and attenuates IR-related inflammation and injury.
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