title: The periodontal pathogen Porphyromonas gingivalis changes the gene expression in vascular smooth muscle cells involving the TGFbeta/Notch signalling pathway and increased cell proliferation.
abstract: BACKGROUND
  Porphyromonas gingivalis is a gram-negative bacterium that causes destructive chronic periodontitis. In addition, this bacterium is also involved in the development of cardiovascular disease. The aim of this study was to investigate the effects of P. gingivalis infection on gene and protein expression in human aortic smooth muscle cells (AoSMCs) and its relation to cellular function.
  
  
  RESULTS
  AoSMCs were exposed to viable P. gingivalis for 24 h, whereafter confocal fluorescence microscopy was used to study P. gingivalis invasion of AoSMCs. AoSMCs proliferation was evaluated by neutral red assay. Human genome microarray, western blot and ELISA were used to investigate how P. gingivalis changes the gene and protein expression of AoSMCs. We found that viable P. gingivalis invades AoSMCs, disrupts stress fiber structures and significantly increases cell proliferation. Microarray results showed that, a total of 982 genes were identified as differentially expressed with the threshold log2 fold change > |1| (adjust p-value <0.05). Using bioinformatic data mining, we demonstrated that up-regulated genes are enriched in gene ontology function of positive control of cell proliferation and down-regulated genes are enriched in the function of negative control of cell proliferation. The results from pathway analysis revealed that all the genes belonging to these two categories induced by P. gingivalis were enriched in 25 pathways, including genes of Notch and TGF-beta pathways.
  
  
  CONCLUSIONS
  This study demonstrates that P. gingivalis is able to invade AoSMCs and stimulate their proliferation. The activation of TGF-beta and Notch signaling pathways may be involved in the bacteria-mediated proliferation of AoSMCs. These findings further support the association between periodontitis and cardiovascular diseases.
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. boxi.zhang@oru.se.
authors.forename: Boxi
authors.initials: B
authors.lastname: Zhang
authors.forename: Ali Ateia
authors.initials: AA
authors.lastname: Elmabsout
authors.forename: Hazem
authors.initials: H
authors.lastname: Khalaf
authors.forename: Vladimir T
authors.initials: VT
authors.lastname: Basic
authors.forename: Kartheyaene
authors.initials: K
authors.lastname: Jayaprakash
authors.forename: Robert
authors.initials: R
authors.lastname: Kruse
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bengtsson
authors.forename: Allan
authors.initials: A
authors.lastname: Sirsjö
mesh_terms: D001011:Aorta / Q000378:metabolism / Q000382:microbiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005881:Gingiva / Q000382:microbiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000235:genetics* / Q000472:pathogenicity; D051880:Receptors, Notch / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051880:Receptors, Notch; D016212:Transforming Growth Factor beta