Identification of inflammatory processes modulator genes using the combined analys...
| Grant number: | 14/18060-2 |
| Support type: | Regular Research Grants |
| Duration: | September 01, 2015 - February 28, 2018 |
| Field of knowledge: | Biological Sciences - Immunology |
| Principal Investigator: | Marcelo de Franco |
| Grantee: | Marcelo de Franco |
| Home Institution: | Instituto Pasteur (IP). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the joints, causing a persistent synovial inflammation and destruction of cartilage and bone. It affects about 1% of the adult population worldwide and is prevalent in women. Its cause is of unknown origin, but we know that is influenced by genetic and environmental factors. Pristane-induced arthritis (PIA) in mice is an experimental model that has been used in many works, because of the similarity to rheumatoid arthritis in humans and its histopathologic and serological characteristics. The strains of mice selected for strong (AIRmax) or weak inflammation (AIRmin) differ in susceptibility to PIA. Studies with these mice have identified significant loci for the experimental arthritis severity on chromosomes 5 and 8 Several inbred strains showed coincident genes in similar experiments, including the participation of micro RNAs (miRNAs) in regulating the expression of these genes. Our hypothesis is that the differential expression of miRNAs in susceptible strains (AIRmax and DBA / 1) and resistant strains (AIRmin and DBA / 2) can lead to modulation of important genes involved in PIA. Thus, the present study addresses whether miRNAs may be involved in the regulation of previously mapped genes and this regulation may affect susceptibility to PIA, making a comparison of heterogeneous strains AIRmax (sensitive) and AIRmin (resistant) with inbred strains DBA / 1 (sensitive) and DBA / 2 (resistant). Furthermore, we will investigate the effect of in vitro inactivation of candidate genes for their effects on the expression of important inflammatory mediators in the development of PIA. The differential expression of miRNAs in these strains will allow better understanding of the genetic architecture and molecular mechanisms involved in this experimental condition. (AU)