Detalhes do projeto

Description

Oral infections are caused by diverse bacterial, viral and fungal pathogens 1, which in many cases are associated with a negative impact on patient's QoL. Indeed, infections trigger an immune response to respond effectively to a pathogen that can result in inflammatory diseases within the oral cavity. In this context, periodontitis, the most common chronic inflammatory disease of human is caused by interactions between periodontopathic bacteria, host immune responses and environmental factors (e.g. smoking)2, representing a major burden on healthcare. Thus, it is important to gain further insight about potential molecular mechanisms involved in PD development and progression. In this regard, TAM receptor tyrosine kinases (RTKs) - TYRO3, AXL and MERTK - together with their ligands, growth arrest-specific 6 (GAS6) and protein S (PROS1) have been implicated in chronic inflammatory diseases like periodontitis3,4. In one study, the Pros1/Tyro3 axis was postulated to protect against periodontitis by modulating STAT/SOCS signalling3. In another study, Porphyromonas gingivalis-mediated PD was reported in mice to result in oral microbial dysbiosis, elevated production of IFN-α by epithelial cells and temporal “immune paralysis” of the gingiva due to a lack of GAS6 and AXL expression in gingival blood vessels4. Based on these findings we can hypothesize that TAM pathway may play a critical role in human PD pathogenesis and severity (by impairing immune response). Taking into consideration the new classification scheme of PD staging and grading5,6, the major goal of this work is to generate molecular data to improve prognosis and clinical management of PD cases. To accomplish this goal, we will use molecular and immunological approaches (illustrated in section 10) to better understand the involvement of the TAM pathway at different stages of PD. Here, we plan to check a possible link between gene expression variability and differential PD susceptibility among individuals as well as to characterize the immune response at different stages of PD as a potential indicator of disease severity.
Data analysis will be essential to shed further light on the relevance of TAM pathway in PD clinical cases and may extrapolate these findings into other inflammatory diseases. Besides supporting prognosis and clinical management of PD, this preliminary work will also serve as proof of concept for larger projects to be prepared and submitted (by both platforms) to future funding proposals.
EstadoTerminado
Data de início/fim efetiva1/09/2128/02/23

Objetivos de Desenvolvimento Sustentável da ONU

Em 2015, os estados membros da ONU acordaram 17 Objetivos de Desenvolvimento Sustentável (ODS) globais para acabar com a pobreza, proteger o planeta e garantir a prosperidade para todos. O projeto contribui para o(s) seguinte(s) ODS:

  • ODS 3 - Boa saúde e bem-estar

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