Grant number: | 16/19963-1 |
Support Opportunities: | Regular Research Grants |
Start date: | March 01, 2017 |
End date: | August 31, 2019 |
Field of knowledge: | Health Sciences - Pharmacy |
Principal Investigator: | Silvia Berlanga de Moraes Barros |
Grantee: | Silvia Berlanga de Moraes Barros |
Host Institution: | Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Abstract
Environmental pollution is a major concern worldwide, specifically, air pollution by particulate matter (PM) that has been linked to the development of many diseases, among them the Atopic Dermatitis (AD). AD is characterized by chronic inflammation of the skin, thus compromising the quality of life of patients. When exposed to PM the skin undergoes structural and functional changes of the epidermal barrier in places of contact or by indirect routes, mechanism responsible in part for the pathophysiology of this disease. Although DA mechanism is extensively studied, the scientific literature lacks information about the AD development mechanism by exposure to PM. In addition, there is no information about the possible action of PM in the exacerbation of AD induced by other causative agents. PM exposure has been associated with heart and lung diseases including lung cancer. Substances presents in PM are known to be genotoxic and the IARC classified the MP as carcinogenic to humans. However, little is known about the possible genotoxic changes that the PM can induce on the skin. The developments of in vitro models that reproduce in one hand the normal epidermis and in other hand the AD are of great value to study pathophysiological processes of the skin and in particular those associated with epidermal changes. These models have the advantage to reconstruct human epidermis from primary human cells, allowing a more direct study of human pathology than with the use of animal models or cell monolayer cultures. The objective of this study is to evaluate the participation of air particulate matter in the development and modulation of atopic dermatitis in reconstructed human skin models (RHE), in order to investigate the molecular and morphological changes caused by skin exposure to these xenobiotics. In parallel will be evaluated the genotoxic changes in the epidermis exposed to PM. To approach these problems normal RHE and induced AD will be produced in the laboratory using established protocols. Histological and immunohistochemical evaluation, expression of genes of interest associated with AD by RT-qPCR and validation by Western Blotting and observation of micronucleus as genotoxicity study method will be performed. The results should contribute not only to the knowledge of the participation of MP in the development and modulation of AD, but also in identifying biomarkers useful for searching for more effective therapies for this disease. (AU)
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