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).

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL098050-03
Application #
8502323
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$230,042
Indirect Cost
$83,518
Name
University of Illinois at Chicago
Department
Type
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Huang, Long Shuang; Natarajan, Viswanathan (2015) Sphingolipids in pulmonary fibrosis. Adv Biol Regul 57:55-63
Ni, Xiuqin; Epshtein, Yulia; Chen, Weiguo et al. (2014) Interaction of integrin ?4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement. J Cell Biochem 115:1187-95
Wolfson, Rachel K; Mapes, Brandon; Garcia, Joe G N (2014) Excessive mechanical stress increases HMGB1 expression in human lung microvascular endothelial cells via STAT3. Microvasc Res 92:50-5
Chen, Jiwang; Tang, Haiyang; Sysol, Justin R et al. (2014) The sphingosine kinase 1/sphingosine-1-phosphate pathway in pulmonary arterial hypertension. Am J Respir Crit Care Med 190:1032-43
Testai, Fernando D; Kilkus, John P; Berdyshev, Evgeny et al. (2014) Multiple sphingolipid abnormalities following cerebral microendothelial hypoxia. J Neurochem 131:530-40
Usatyuk, Peter V; Fu, Panfeng; Mohan, Vijay et al. (2014) Role of c-Met/phosphatidylinositol 3-kinase (PI3k)/Akt signaling in hepatocyte growth factor (HGF)-mediated lamellipodia formation, reactive oxygen species (ROS) generation, and motility of lung endothelial cells. J Biol Chem 289:13476-91
Adyshev, Djanybek M; Elangovan, Venkateswaran Ramamoorthi; Moldobaeva, Nurgul et al. (2014) Mechanical stress induces pre-B-cell colony-enhancing factor/NAMPT expression via epigenetic regulation by miR-374a and miR-568 in human lung endothelium. Am J Respir Cell Mol Biol 50:409-18
Huang, Long Shuang; Mathew, Biji; Li, Haiquan et al. (2014) The mitochondrial cardiolipin remodeling enzyme lysocardiolipin acyltransferase is a novel target in pulmonary fibrosis. Am J Respir Crit Care Med 189:1402-15
Wang, Lichun; Sammani, Saad; Moreno-Vinasco, Liliana et al. (2014) FTY720 (s)-phosphonate preserves sphingosine 1-phosphate receptor 1 expression and exhibits superior barrier protection to FTY720 in acute lung injury. Crit Care Med 42:e189-99
Makarenko, Vladislav V; Usatyuk, Peter V; Yuan, Guoxiang et al. (2014) Intermittent hypoxia-induced endothelial barrier dysfunction requires ROS-dependent MAP kinase activation. Am J Physiol Cell Physiol 306:C745-52

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