RGD Reference Report - Time-Dependent Alterations of VEGF and Its Signaling Molecules in Acute Lung Injury in a Rat Model of Sepsis. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Time-Dependent Alterations of VEGF and Its Signaling Molecules in Acute Lung Injury in a Rat Model of Sepsis.

Authors: Jesmin, S  Zaedi, S  Islam, AM  Sultana, SN  Iwashima, Y  Wada, T  Yamaguchi, N  Hiroe, M  Gando, S 
Citation: Jesmin S, etal., Inflammation. 2011 Apr 29.
RGD ID: 5684427
Pubmed: PMID:21528367   (View Abstract at PubMed)
DOI: DOI:10.1007/s10753-011-9337-1   (Journal Full-text)

Molecular mechanisms of sepsis-associated acute lung injury (ALI) are poorly defined. Since vascular endothelial growth factor (VEGF) is a potent vascular permeability and mitogenic factor, it might contribute to the development of ALI in sepsis. Thus, using lipopolysaccharide (LPS)-induced (15 mg/kg, intraperitoneal) endotoxemic rat model, we studied the timeline (1, 3, 6, and 10 h) of pulmonary VEGF expression and its signaling machinery. Levels of pulmonary VEGF and its angiogenic-mediating receptor, Flk-1, were downregulated by LPS in a time-dependent manner; levels of plasma VEGF and its permeability-mediating receptor, Flt-1, in contrast, was upregulated with time. In addition, blockade of Flt-1 could improve the downregulated pulmonary VEGF level and attenuate the elevated plasma and pulmonary levels of TNF-alpha, followed by improvement of arterial oxygenation and wet-to-dry weight ratio of the lung. Expression of signaling, pro- and or apoptotic factors after LPS administration were as follows: phosphorylated Akt, a downstream molecule was downregulated time dependently; endothelial nitric oxide synthase levels were significantly reduced; pro-apoptotic markers caspase 3 and Bax were upregulated whereas levels of Bcl-2 were downregulated. The present findings show that VEGF may play a role through the expression of Flt-1 in LPS-induced ALI. Moreover, downregulation of VEGF signaling cascade may account for LPS-induced apoptosis and impaired physiological angiogenesis in lung tissues, which in turn may contribute to the development of ALI induced by LPS.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FLT1HumanAcute Lung Injury  ISOFlt1 (Rattus norvegicus)associated with EndotoxemiaRGD 
Flt1RatAcute Lung Injury  IMP associated with EndotoxemiaRGD 
Flt1MouseAcute Lung Injury  ISOFlt1 (Rattus norvegicus)associated with EndotoxemiaRGD 
KDRHumanAcute Lung Injury  ISOKdr (Rattus norvegicus)associated with Endotoxemia more ...RGD 
KdrRatAcute Lung Injury  IEP associated with Endotoxemia more ...RGD 
KdrMouseAcute Lung Injury  ISOKdr (Rattus norvegicus)associated with Endotoxemia more ...RGD 
VEGFAHumanAcute Lung Injury  ISOVegfa (Rattus norvegicus)associated with Endotoxemia more ...RGD 
VegfaRatAcute Lung Injury  IEP associated with Endotoxemia more ...RGD 
VegfaMouseAcute Lung Injury  ISOVegfa (Rattus norvegicus)associated with Endotoxemia more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Flt1  (Fms related receptor tyrosine kinase 1)
Kdr  (kinase insert domain receptor)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Flt1  (FMS-like tyrosine kinase 1)
Kdr  (kinase insert domain protein receptor)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
FLT1  (fms related receptor tyrosine kinase 1)
KDR  (kinase insert domain receptor)
VEGFA  (vascular endothelial growth factor A)


Additional Information