Evaluation of IL7 as key molecule related with glycemic and immune alterations in type 2 Diabetes Mellitus and Periodontitis

• Grant number: 20/11651-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2021
• End date: August 31, 2024
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Raquel Mantuaneli Scarel Caminaga
• Grantee: Bárbara Roque da Silva
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

It has been found more frequently patients affected by a combination of Type 2 Diabetes Mellitus (T2DM), Dyslipidemia, and Periodontitis (P). Evidence in the literature is increasing in demonstrating interactions between T2DM, Dyslipidemia, immune system dysfunction, and Periodontitis. For a better understanding of such interactions, and to know molecules with a key role on them, it is valuable to develop studies utilizing animal models, mainly murine. It is also important to better understand the interaction between the individual's oral and systemic health. The importance of Interleukin 7 (IL-7) in the immune system is undoubtable, but few studies investigated its involvment in the modulation of T2DM and Periodontitis. Data from the literature and our previous results with patients affected by T2DM and Periodontitis support our hypothesis that IL7, by means of TNFA, is a key molecule for these pathologies. The general objective of this pre-clinical study is to carry out the evaluation of IL-7 as a key molecule for glycemic and immunological changes in T2DM and Periodontitis, occurring as comorbidities, or each one isolated. Murine model methodology: 48 male C57BL/ 6J mice will be evaluated in each group: DM, Periodontitis, DM + P, and control. The influence of the treatment of DM with Metformin will also be evaluated, through the inclusion of 2 more groups: DM-Metf, and DM-Metf + P, in the same experimental periods. DM will be induced by the combination of high-fat diet and streptozotocin injection; and Periodontitis will be induced by a combination of ligature and infection by Porphyromonas gingivalis. Twelve animals in each group will be euthanized in the experimental periods: Zero, 7, 14, and 21 days of treatment. Periodontal bone loss in animals will be assessed by micro-CT. The behavior of the key IL-7 molecule, in addition to TNFA, and IL-10 will be evaluated in all groups and periods through: (I) morphology (histological and stereometric, focusing mainly on inflammatory aspects); (II) evaluation of systemic transcriptional levels (mRNA in murine blood), systemic translational levels (protein levels in murine blood); in addition to periodontal transcriptional (murine gingiva mRNA) and translational (murine gingiva immunohistochemistry for localization and quantification of these proteins). Linear and/or multiple logistic regressions will be performed, in addition to correlation analyzes, of the transcriptional and translational levels of these molecules depending on the glycemic, lipid, and periodontal profiles, intra- and inter-groups in the different periods. Through this study we will deepen the understanding of the pathogenic interaction between T2DM and Periodontitis. This will allow to know the transcriptional and translational behavior of IL-7 in an animal model of Diabetes and/or Periodontitis, in order to have parameters for, in a subsequent study, to carry out functional studies modulating the levels of IL-7 and verifying its effects. (AU)