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Proteinase-Activated Receptors (PARs) in the dentin-pulp complex: identification, modulation and signal tranduction in caries disease


The many mechanisms whereby proteolytic enzymes can regulate cell functions have been only elucidated in the late 60's, when the generation or degradation of active polypeptides, was established. Since that time, proteinases have taken on a new life as hormone-like signal messengers. The search for a receptor that can be activated through the hydrolysis of its extracellular portion and subsequently initiate a signaling cascade brought to the literature a special kind of G-protein-coupled receptors (GPCRs), named Protease-Activated Receptors (PARs). These receptors are responsible for mediating several important responses processes, such as: hemostasis, thrombosis, inflammation, embryonic development and the pathogenesis of many types of cancer. There are, so far, no descriptions about the presence or the role of these receptors family in the dentin-pulp complex. The aim of this project is to evaluate the presence and modulation of PARs in three different experimental models: odontoblastic cells, adult pulp tissue and odontoblasts derived from adult stem cells. For this purpose will be performed gene microarray assay, gene and protein qPCR assays and enzyme kinetics experiments. This research project will contribute in unparalleled manner to a better understanding of caries process. (AU)

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Scientific publications (9)
(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)
CARVALHO, RAFAEL GUZELLA; PALACIO ALVAREZ, MARCELA MACIEL; OLIVEIRA, THALES DE SA; POLASSI, MACKELER RAMOS; VILHENA, FABIANO VIEIRA; ALVES, FLAVIO LOPES; NAKAIE, CLOVIS RYUICHI; NASCIMENTO, FABIO DUPART; PERLATTI D'ALPINO, PAULO HENRIQUE; DOS SANTOS TERSARIOL, IVARNE LUIS. The interaction of sodium trimetaphosphate with collagen I induces conformational change and mineralization that prevents collagenase proteolytic attack. Dental Materials, v. 36, n. 6, p. E184-E193, . (13/05822-9)
DE SOUSA, J. P.; CARVALHO, R. G.; BARBOSA-MARTINS, L. F.; TORQUATO, R. J. S.; MUGNOL, K. C. U.; NASCIMENTO, F. D.; TERSARIOL, I. L. S.; PUPPIN-RONTANI, R. M.. The Self-Assembling Peptide P-11-4 Prevents Collagen Proteolysis in Dentin. JOURNAL OF DENTAL RESEARCH, v. 98, n. 3, p. 347-354, . (13/05822-9, 14/22899-8, 15/03964-6, 15/12660-0)
ALVAREZ, M. M. P.; MOURA, G. E.; MACHADO, M. F. M.; VIANA, G. M.; DE SOUZA COSTA, C. A.; TJADERHANE, L.; NADER, H. B.; TERSARIOL, I. L. S.; NASCIMENTO, F. D.. PAR-1 and PAR-2 Expression Is Enhanced in Inflamed Odontoblast Cells. JOURNAL OF DENTAL RESEARCH, v. 96, n. 13, p. 1518-1525, . (13/05822-9, 15/03964-6)
PERLATTI D'ALPINO, PAULO HENRIQUE; DINIZ DE DANTAS MOURA, GIOCONDA EMANUELLA; DE ARRUDA BARBOSA, SILVANA COELHO; MARQUES, LYGIA DE AZEVEDO; EBERLIN, MARCOS NOGUEIRA; NASCIMENTO, FABIO DUPART; DOS SANTOS TERSARIOL, IVARNE LUIS. Differential cytotoxic effects on odontoblastic cells induced by self-adhesive resin cements as a function of the activation protocol. Dental Materials, v. 33, n. 12, p. 1402-1415, . (13/05822-9)
DAMASCENO, IGOR Z.; MELO, KATIA R. B.; NASCIMENTO, FABIO D.; SOUZA, DAIANNE S. P.; ARAUJO, MARIANA S.; SOUZA, SINVAL E. G.; SAMPAIO, MISAKO U.; NADER, HELENA B.; TERSARIOL, IVARNE L. S.; MOTTA, GUACYARA. Bradykinin Release Avoids High Molecular Weight Kininogen Endocytosis. PLoS One, v. 10, n. 3, . (13/05822-9)
VERONEZ, CAMILA LOPES; NASCIMENTO, FABIO D.; MELO, KATIA R. B.; NADER, HELENA B.; TERSARIOL, IVARNE L. S.; MOTTA, GUACYARA. The Involvement of Proteoglycans in the Human Plasma Prekallikrein Interaction with the Cell Surface. PLoS One, v. 9, n. 3, . (13/05822-9, 09/13160-0)
CARRILHO, MARCELA R.; SCAFFA, POLLIANA; OLIVEIRA, VITOR; TJADERHANE, LEO; TERSARIOL, IVARNE L.; PASHLEY, DAVID H.; TAY, FRANKLIN; NASCIMENTO, FABIO D.. Insights into cathepsin-B activity in mature dentin matrix. ARCHIVES OF ORAL BIOLOGY, v. 117, . (16/07996-2, 13/05822-9, 11/12226-8)
PALACIO ALVAREZ, MARCELA MACIEL; DE CARVALHO, RAFAEL GUZELLA; DE ARRUDA BARBOSA, SILVANA COELHO; POLASSI, MACKELER RAMOS; NASCIMENTO, FABIO DUPART; PERLATTI D'ALPINO, PAULO HENRIQUE; DOS SANTOS TERSARIOL, IVARNE LUIS. Oxidative stress induced by self-adhesive resin cements affects gene expression, cellular proliferation and mineralization potential of the MDPC-23 odontoblast-like cells. Dental Materials, v. 35, n. 4, p. 606-616, . (13/05822-9, 15/03964-6)
VIDAL, C. M. P.; TJADERHANE, L.; SCAFFA, P. M.; TERSARIOL, I. L.; PASHLEY, D.; NADER, H. B.; NASCIMENTO, F. D.; CARRILHO, M. R.. Abundance of MMPs and Cysteine Cathepsins in Caries-affected Dentin. JOURNAL OF DENTAL RESEARCH, v. 93, n. 3, p. 269-274, . (13/05822-9, 11/12226-8, 09/13652-0)

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