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

BackgroundPorphyromonas 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.ResultsAoSMCs 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.ConclusionsThis 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.

Genome-wide transcriptome induced by Porphyromonas gingivalis LPS supports the notion of host-derived periodontal destruction and its association with systemic diseases

“…Our data complement recent investigations, which applied microarray technology and different cell types, stimuli and exposure durations. [48][49][50] For instance, Yu et al investigated human macrophages isolated from buffy coats that were challenged with 10 mg/ml LPS or live Pg for 2 h. 48 The authors detected 575 differentially regulated genes in the LPS group based on three independent macrophage experiments, and identified 13 pathways, most of which correspond to host immune defense. 48 The present study identified >900 genes, >2149 upstream regulators and 200 canonical pathways implicated in the Pg-induced immune response.…”

Biological links in periodontitis and rheumatoid arthritis: Discovery via text‐mining PubMed abstracts

“…Recent evidence shows the M1 phenotype macrophages are the main source in NOTCH molecules in RA and play an important role in the chronicity of synovial inflammation . On the other hand, P. gingivalis infection increases NOTCH signaling in aortic smooth muscle . It is plausible that by a similar mechanism of NOTCH signaling, periodontal bacteria may aggravate the inflammatory process in RA.…”

“…63,64 On the other hand, P. gingivalis infection increases NOTCH signaling in aortic smooth muscle. 65 It is plausible that by a similar mechanism of NOTCH signaling, periodontal bacteria may aggravate the inflammatory process in RA. immune responses.…”

Cellular Response Mechanisms in Porphyromonas gingivalis Infection

“…In correla tion, interaction between P. gingivalis and human blood cells, for example, platelets, neutro phils, monocytes, and T-cells, is mainly mediated by TLR2 and has dramatic inflammatory and immunomodulatory effects, including cellular aggregation, oxygen radical production, lowdensity lipoprotein (LDL) oxidation, and release and degradation of cytokines. Furthermore, P. gingivalis changes the expression of more than thousand genes in vascular smooth muscle cells [84]. For example, P. gingivalis upregulates genes involved in proliferation, for example, the TGFβ1 pathway and production of matrix proteins, but downregulates pro-inflammatory genes, such as those involved in IL-1β, IL-6, and CXCL8 production.…”