The Pre-Clinical Animal Models Core (Core C), under the leadership of Drs. Yuan and Moreno, is designed to provide PPG investigators with rigorously defined and reproducible murine models of acute lung injury (ALI), ventilation-induced lung injury (VILI) and radiation-induced lung injury (RILI). The Core will advance three principal objectives with the first objective to provide a complete range of expertise, training, equipment, and data analysis tools to extensively study and characterize the role of sphingolipids in murine models of lung injury. Using published protocols and parameters from a variety of ALI, VILI and RILI models (mice, rats, dogs), we will employ state-of-the-art techniques to characterize the role of sphingolipids in inflammatory lung injury as well as the effects of specific interventions in order to provide insight into the efficacy and mechanisms of novel therapeutic strategies and to facilitate the translation of basic research to the clinical arena. To this end, the core will provide quantitative measurements of vascular permeability (Kfc) and albumin content, inflammation (tissue myeloperoxidase, inflammatory cells), edema (Evans blue dye extravasation) and specific biomarkers. The second objective is to house and care for the geneticallyengineered mice utilized in this PPG and to generate novel transgenic mice. The third objective will be to utilize RNA silencing strategies (siRNA), targeting the lung endothelium (ACE conjugated) or liposome encapsulated and the use of pharmacologic agonists or antagon-ists/inhibitors for SIP receptors as potential therapeutic strategies/approaches for acute lung injury, mechanical ventilation or radiation-induced pneumonitis lung injury models. The core will have full access to and will utilize resources available at the University of Illinois at Chicago Small Animal Imaging Core (including MRI and optical imaging).
The pre-clinical studies are essential for validation of the in vitro observations from the four project leaders of this PPG. Core C also is critical in the developing of novel therapeutic targets and strategies that eventually will lead to translational research and intervention strategies to all the disorders studied here, acute Lung Injury, mechanical ventilation induced lung injury and radiation induced pneumonitis.
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|Natarajan, Viswanathan; Ha, Alison W; Dong, Yangbasai et al. (2017) Expression profiling of genes regulated by sphingosine kinase1 signaling in a murine model of hyperoxia induced neonatal bronchopulmonary dysplasia. BMC Genomics 18:664|
|Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani et al. (2017) Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase. Adv Biol Regul 63:156-166|
|Rizzo, Alicia N; Dudek, Steven M (2017) Endothelial Glycocalyx Repair: Building a Wall to Protect the Lung during Sepsis. Am J Respir Cell Mol Biol 56:687-688|
|Huang, Long Shuang; Jiang, Peiyue; Feghali-Bostwick, Carol et al. (2017) Lysocardiolipin acyltransferase regulates TGF-? mediated lung fibroblast differentiation. Free Radic Biol Med 112:162-173|
|Sysol, Justin R; Natarajan, Viswanathan; Machado, Roberto F (2016) PDGF induces SphK1 expression via Egr-1 to promote pulmonary artery smooth muscle cell proliferation. Am J Physiol Cell Physiol 310:C983-92|
|Camp, Sara M; Chiang, Eddie T; Sun, Chaode et al. (2016) ""Pulmonary Endothelial Cell Barrier Enhancement by Novel FTY720 Analogs: Methoxy-FTY720, Fluoro-FTY720, and ?-Glucuronide-FTY720"". Chem Phys Lipids 194:85-93|
|Fu, Panfeng; Ebenezer, David L; Berdyshev, Evgeny V et al. (2016) Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated Lamellipodia Formation in Lung Endothelium. J Biol Chem 291:27187-27203|
|Jiang, Ying; Sverdlov, Maria S; Toth, Peter T et al. (2016) Phosphatidic Acid Produced by RalA-activated PLD2 Stimulates Caveolae-mediated Endocytosis and Trafficking in Endothelial Cells. J Biol Chem 291:20729-38|
|Black, Katharine E; Berdyshev, Evgeny; Bain, Gretchen et al. (2016) Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis. FASEB J 30:2435-50|
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