ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 63 citations in OpenAlex.
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- A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome.Annual review of physiology · 2024Review
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- Identification of S100A9 as a Potential Inflammation-Related Biomarker for Radiation-Induced Lung Injury.Journal of clinical medicine · 2023Article
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- Pathological observation of the effects of exposure to radioactive microparticles on experimental animals.Journal of radiation research · 2022Review
- eNAMPT Is a Novel Damage-associated Molecular Pattern Protein That Contributes to the Severity of Radiation-induced Lung Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
- Involvement of eNAMPT/TLR4 signaling in murine radiation pneumonitis: protection by eNAMPT neutralization.Translational research : the journal of laboratory and clinical medicine · 2022Article
- eNAMPT Neutralization Preserves Lung Fluid Balance and Reduces Acute Renal Injury in Porcine Sepsis/VILI-Induced Inflammatory Lung Injury.Frontiers in physiology · 2022Article
- MRSA-induced endothelial permeability and acute lung injury are attenuated by FTY720 S-phosphonate.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Sphingolipids as a Novel Therapeutic Target in Radiation-Induced Lung Injury.Cell biochemistry and biophysics · 2021Review
- My Journey in Academia as a Lipid Biochemist.Cell biochemistry and biophysics · 2021Review
- Lysophospholipids in Lung Inflammatory Diseases.Advances in experimental medicine and biology · 2021Article
- Impact of Local High Doses of Radiation by Neutron Activated Mn Dioxide Powder in Rat Lungs: Protracted Pathologic Damage Initiated by Internal Exposure.Biomedicines · 2020Article
- Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways.International journal of molecular sciences · 2020Review
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- The Predictive Value of MLR for Radiation Pneumonia During Radiotherapy of Thoracic Tumor Patients.Cancer management and research · 2020Article
- Metabolomic Analysis Reveals Unique Biochemical Signatures Associated with Protection from Radiation Induced Lung Injury by Lack ofMetabolites · 2019Article
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components serve as modulators and novel therapeutic targets of RILI. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to sphingosine 1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage fluid, and lung tissue. Mice with a targeted deletion of SphK1 (SphK1(-/-)) or with reduced expression of S1P receptors (S1PR1(+/-), S1PR2(-/-), and S1PR3(-/-)) exhibited marked RILI susceptibility. Finally, studies of 3 potent vascular barrier-protective S1P analogs, FTY720, (S)-FTY720-phosphonate (fTyS), and SEW-2871, identified significant RILI attenuation and radiation-induced gene dysregulation by the phosphonate analog, fTyS (0.1 and 1 mg/kg i.p., 2×/wk) and to a lesser degree by SEW-2871 (1 mg/kg i.p., 2×/wk), compared with those in controls. These results support the targeting of S1P signaling as a novel therapeutic strategy in RILI.
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