Down‐regulation of epidermal growth factor receptor‐dependent signaling by <i>Porphyromonas gingivalis</i> lipopolysaccharide in life‐expanded human gingival fibroblasts

Quinchia-Rios, Beatriz H.; Guerrero, Mario; Abozeid, Sara; Bainbridge, Brian W.; Darveau, Richard P.; Compton, Teresa; Bertics, Paul J.

doi:10.1111/j.1600-0765.2007.01029.x

Cited by 10 publications

(8 citation statements)

References 68 publications

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“…It was suggested that this phenomenon is directly related to the fact that both epidermal growth factor and LPS activate the MAPKs to modulate cell proliferation, cell survival, and the release of inflammatory mediators. The observed alterations in EGF signaling caused by P. gingivalis LPS may be mediated by an array of events, including, among other possibilities, the differential recruitment and altered kinetics of activation of upstream mediators in response to LPS and EGF (72). The effect observed here cannot be associated with LPS activity, since no decrease in EGF activity following incubation with LPS-positive ATCC 33277 ⌬ppad or W83 ⌬ppad P. gingivalis mutants was observed.…”

Section: Discussionmentioning

confidence: 45%

“…It has been previously shown that P. gingivalis lipopolysaccharide (LPS) modulates the regenerative effect of EGF via downregulation of EGFR-dependent signaling (72). It was suggested that this phenomenon is directly related to the fact that both epidermal growth factor and LPS activate the MAPKs to modulate cell proliferation, cell survival, and the release of inflammatory mediators.…”

Section: Discussionmentioning

confidence: 99%

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Inactivation of Epidermal Growth Factor by Porphyromonas gingivalis as a Potential Mechanism for Periodontal Tissue Damage

et al. 2013

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f Porphyromonas gingivalis is a Gram-negative bacterium associated with the development of periodontitis. The evolutionary success of this pathogen results directly from the presence of numerous virulence factors, including peptidylarginine deiminase (PPAD), an enzyme that converts arginine to citrulline in proteins and peptides. Such posttranslational modification is thought to affect the function of many different signaling molecules. Taking into account the importance of tissue remodeling and repair mechanisms for periodontal homeostasis, which are orchestrated by ligands of the epidermal growth factor receptor (EGFR), we investigated the ability of PPAD to distort cross talk between the epithelium and the epidermal growth factor (EGF) signaling pathway. We found that EGF preincubation with purified recombinant PPAD, or a wild-type strain of P. gingivalis, but not with a PPAD-deficient isogenic mutant, efficiently hindered the ability of the growth factor to stimulate epidermal cell proliferation and migration. In addition, PPAD abrogated EGFR-EGF interaction-dependent stimulation of expression of suppressor of cytokine signaling 3 and interferon regulatory factor 1. Biochemical analysis clearly showed that the PPAD-exerted effects on EGF activities were solely due to deimination of the C-terminal arginine. Interestingly, citrullination of two internal Arg residues with human endogenous peptidylarginine deiminases did not alter EFG function, arguing that the C-terminal arginine is essential for EGF biological activity. Cumulatively, these data suggest that the PPAD-activity-abrogating EGF function in gingival pockets may at least partially contribute to tissue damage and delayed healing within P. gingivalis-infected periodontia.

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Section: Discussionmentioning

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Inactivation of Epidermal Growth Factor by Porphyromonas gingivalis as a Potential Mechanism for Periodontal Tissue Damage

et al. 2013

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“…Independent of the innate host response, periodontal pathogens target and disrupt various host cellular pathways including tissue homeostasis and repair that are of paramount importance to the pathogenesis of periodontal disease (Darveau, ; Pyrc et al., ; Quinchia‐Rios et al., ). Extracellular signal‐related kinases (Erks) are one of the three main families of MAP kinases.…”

Section: Discussionmentioning

confidence: 99%

“…This disrupts the activation of ERK pathway consequently leading to reduced epidermal cell proliferation. Similarly, Pg LPS is known to inhibit EGF‐mediated signalling by reducing the phosphorylation of ERK2 (MAPK1) and other components of the MAPK signalling cascade including ERK1, p38 MAPK and cyclic‐AMP response element binding (CREB) (Quinchia‐Rios et al., ). We identify and demonstrate that miR‐24 and miR‐27a and miR‐30 target MAPK1 and exhibit antagonistic, yet differential expression in diseased obese and non‐obese gingival tissues.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of human miRNAs and increased prevalence of HHV miRNAs in obese periodontitis subjects

Naqvi

Brambila

Martínez

et al. 2019

J Clinic Periodontology

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Aim: To evaluate human and herpesvirus-encoded microRNA (miRNA) expression in healthy and diseased gingiva of obese and non-obese subjects and compare the impact of localized and systemic inflammation on human miRNA profiles. Material and methods: Healthy and inflamed gingival biopsies were collected from obese and non-obese subjects. Human and herpesvirus miRNA expression was quantified using quantitative PCR. Predicted targets of dysregulated miRNAs were identified using bioinformatics analysis, validated by dual luciferase assays and their expression assessed in healthy and diseased tissues. Results: Our results show differential expression of miRNAs in both diseased groups compared to healthy counterparts. MMP-16 is identified as a novel target of miRNAs altered in disease. Expression analysis of genes predicted as target of differentially expressed miRNAs show significant changes in disease compared with healthy tissues. Finally, quantitation of four herpesvirus derived viral miRNAs show that expression and prevalence of herpesvirus miRNAs in diseased gingiva of obese subjects. Conclusion: Our findings show that miRNA (both cellular and virus) expression are differentially responsive to local and systemic inflammation. Some of these miRNAs can modulate key cellular genes with direct consequences on inflammatory pathways suggesting their impact on oral tissue transcriptome and functions.

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“…gingipains, fimbriae, and lipopolysaccharide [LPS]) may disturb the EGF signaling pathway. Indeed, in a model of gingival fibroblasts, purified LPS from P. gingivalis led to a loss of activation of secondary signals depending on the presence of EGF, notably ERK1/2 and p38 kinase, with downstream consequences for the phosphorylation of the transcription factor cAMP response element-binding [17]. In addition to LPS and other known virulence factors, one bacterial enzyme, peptidyl arginine deiminase (PADPg), a unique feature from P. gingivalis , is emerging [18].…”

Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis and its lipopolysaccharide differently modulate epidermal growth factor–dependent signaling in human gingival epithelial cells

Elkaïm

Bugueno

Benkirane‐Jessel

et al. 2017

Journal of Oral Microbiology

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Periodontitis is an inflammatory disease induced by pathogenic bacteria such as Porphyromonas gingivalis. Little is known about epidermal growth factor (EGF) signals in human gingival epithelial cells (HGEC), which are major targets of P. gingivalis, and how the expression of proteins participating in EGF signaling—that is, EGF-receptor (EGFR), suppressor of cytokine signaling-3 (SOCS-3), interferon regulatory factor-1 (IRF-1), and signal transducers and activators of transcription (STAT-3)—are modified. This study aimed to assess the effects of P. gingivalis and its purified lipopolysaccharide (LPS-Pg) on EGF signaling. HGEC were infected for 2 h in a dose-dependent manner with P. gingivalis and with heat-killed P. gingivalis, and activated for 2 and 24 h by 1 µg/mL of purified LPS-Pg. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to measure mRNA and protein levels for SOCS-3, IRF-1 EGF, EGFR, and STAT-3. The tyrosine-phosphorylation status of STAT-3 was also examined. The results showed that infection of HGEC cells with P. gingivalis, but not with heat-killed P. gingivalis, led to significant reductions in expression levels of mRNAs and proteins for SOCS-3, IRF-1, and EGFR, while LPS-Pg over time significantly increased the expression of these mRNAs and proteins. Tyrosine-phosphorylation of STAT-3 was significantly increased during infection with P. gingivalis and activation by LPS-Pg but not modified during infection with heat-killed P. gingivalis. This study highlights that P. gingivalis and its purified LPS differentially modulated the expression of proteins (SOCS-3, IRF-1, EGFR, and STAT-3) interfering with EGF signaling.

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Down‐regulation of epidermal growth factor receptor‐dependent signaling by Porphyromonas gingivalis lipopolysaccharide in life‐expanded human gingival fibroblasts

Cited by 10 publications

References 68 publications

Inactivation of Epidermal Growth Factor by Porphyromonas gingivalis as a Potential Mechanism for Periodontal Tissue Damage

Inactivation of Epidermal Growth Factor by Porphyromonas gingivalis as a Potential Mechanism for Periodontal Tissue Damage

Dysregulation of human miRNAs and increased prevalence of HHV miRNAs in obese periodontitis subjects

Porphyromonas gingivalis and its lipopolysaccharide differently modulate epidermal growth factor–dependent signaling in human gingival epithelial cells

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