title: Characterization of Prox1 and VEGFR-3 expression and lymphatic phenotype in normal organs of mice lacking p50 subunit of NF-κB.
abstract: OBJECTIVE
  Inflammation and NF-κB are highly associated with lymphangiogenesis but the underlying mechanisms remain unclear. We recently established that activated NF-κB p50 subunit increases expression of the main lymphangiogenic mediators, VEGFR-3 and its transcriptional activator, Prox1. To elucidate the role of p50 in lymphatic vasculature, we compared LVD and phenotype in p50 KO and WT mice.
  
  
  METHODS
  Normal tissues from KO and WT mice were stained for LYVE-1 to calculate LVD. VEGFR-3 and Prox1 expressions were analyzed by immunofluorescence and qRT-PCR.
  
  
  RESULTS
  Compared with WT, LVD in the liver and lungs of KO mice was reduced by 39% and 13%, respectively. This corresponded to 25-44% decreased VEGFR-3 and Prox1 expression. In the MFP, LVD was decreased by 18% but VEGFR-3 and Prox1 expression was 80-140% higher than in WT. Analysis of p65 and p52 NF-κB subunits and an array of inflammatory mediators showed a significant increase in p50 alternative pathways in the MFP but not in other organs.
  
  
  CONCLUSIONS
  These findings demonstrate the role of NF-κB p50 in regulating the expression of VEGFR-3, Prox1 and LVD in the mammary tissue, liver, and lung.
authors.affiliation: Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9626, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Flister
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Volk
authors.forename: Sophia
authors.initials: S
authors.lastname: Ran
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D042583:Lymphangiogenesis / Q000235:genetics* / Q000502:physiology*; D042601:Lymphatic Vessels / Q000033:anatomy & histology / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000172:deficiency* / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics* / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; D018836:Inflammation Mediators; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D040321:Vascular Endothelial Growth Factor Receptor-3