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Role of the induced miRNAs after the aryl hydrocarbon receptor (AhR) activation and their functions in the pathogenesis of rheumatoid arthritis

Grant number: 12/02438-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2012
Effective date (End): May 31, 2016
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Fernando de Queiroz Cunha
Grantee:Paula Barbim Donate Yabuta
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

RA is a systemic autoimmune disorder mainly characterized by an intense inflammatory process in the synovial tissue. The T CD4+ lymphocytes, specially the Th17 subtype, have a central role in the induction and progression of the disease. It has been demonstrated that the activation of the aryl hydrocarbon receptor (AhR), an intracellular protein that bound with high affinity to the environmental toxicant, including those components found in the cigarettes smoke, participate in the differentiation and activation of Th17 cells. MicroRNAs (miRNAs) are small non-coding RNA molecules that modulate the expression of multiple protein-encoding genes at the post-transcriptional level. Their contributions in the differentiation and activation processes of immune cells, and also in the pathogenesis of diseases, are of great interest and have been studied. Based on this information, our hypothesis is that after the AhR activation, specific miRNAs are induced, and control messengers RNAs implicated in the differentiation and activation of Th17 lymphocytes. The miRNAs would be a possible mechanism by which the AhR exacerbates the characteristic inflammatory process in arthritis. In this way, the objective of this project is to determine the miRNAs induced after the AhR activation, and their roles in the RA pathogenesis. The microarray technology will be a powerful tool used to investigate the miRNAs expression and their targets in Th17 cells. Moreover, functional assays will be performed to establish the functions of the selected miRNAs. Our results will contribute to a better understanding of the genetics and molecular basis of the AhR activation, related to the development and activation of Th17 cells in RA, and might contribute to the development of a new therapy for the disease.