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The role of Porphyromonas gingivalis-Nucleoside diphosphate kinase in epigenetic modulation of P2X7 receptor

Grant number: 15/20954-4
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): February 01, 2016
Effective date (End): April 30, 2016
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal researcher:Carlos Ferreira dos Santos
Grantee:Ana Carolina Morandini Ramos
Supervisor abroad: Ozlem Yilmaz
Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
Research place: Medical University of South Carolina (MUSC), United States  
Associated to the scholarship:13/16113-9 - Signaling by purinergic receptor P2X7 and histone deacetylases in the innate immune response of human periodontal fibroblasts: implications in the pathogenesis of periodontitis, BP.PD


Porphyromonas gingivalis is one of the pathogens most commonly associated with chronic periodontitis, being known as a keystone-pathogen in this inflammatory disease. One of P. gingivalis virulence factors is a homologous enzyme nucleoside diphosphate kinase (NDK), which is secreted by P. gingivalis. NDK is able to cleave extracellular ATP (eATP), suppressing eATP-induced apoptosis in a P2X7 receptor and reactive oxygen species-dependent manner, thus contributing to the persistence of the bacteria in gingival epithelial cells. Among the mechanisms that regulate host-microbial interactions it has been widely discussed epigenetic modulations, such as histone deacetylation promoted by HDAC enzymes. Interestingly, data obtained during our present project show that the expression and functionality of P2X7 receptors was decreased in gingival fibroblasts which have been silenced for HDAC1 and were infected by P. gingivalis, suggesting that HDAC1 is involved, at least in part with P2X7 receptors function in these cells. The epithelial cells have recently been recognized as key host cells in the epigenetic regulation of periodontal health and disease and indeed they stand as physiologically relevant cell type to study the epigenetic effect of oral bacteria on oral tissues. Our aim in this BEPE purpose is to investigate whether epigenetic modulation by HDAC1 may be dependent on Pg-NDK. For this, we propose to investigate the role of Pg-NDK in the expression and functionality of P2X7 receptor in gingival epithelial cells silenced or not for HDAC1.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MORANDINI, ANA CAROLINA; SANTOS, CARLOS F.; YILMAZ, OEZLEM. Role of epigenetics in modulation of immune response at the junction of host-pathogen interaction and danger molecule signaling. PATHOGENS AND DISEASE, v. 74, n. 7, . (13/16113-9, 15/20954-4)
GABRIELE, LILIAN GOBBO; MORANDINI, ANA CAROLINA; DIONISIO, THIAGO JOSE; SANTOS, CARLOS FERREIRA. Angiotensin II Type 1 Receptor Knockdown Impairs Interleukin-1 beta-Induced Cytokines in Human Periodontal Fibroblasts. Journal of Periodontology, v. 88, n. 1, p. E1-E11, . (13/16113-9, 15/03965-2, 15/20954-4)

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