The mTOR signaling pathway can be activated by several molecules including insulin and IGF-1, besides it can also be activated after binding of immune system receptors as T cells (TCR), B cells (BCR) and toll-like receptors (TLR). There are two mTOR complexes, mTORC1 and mTORC2, that differ in crucial components of the signalization, as the presence of raptor and rictor respectively. Recently, it was demonstrated that Th1 and Th17 polarization required mTORC1 activation and the Th2 differentiation required mTORC2 activation. Taking into consideration that the macrophage differentiation to M1 depends on IFN-g and to M2 depends on IL-4 and IL-13, Th1 and Th2 cytokines respectively, we questioned whether M1/M2 polarization could depend on mTORC1 and/or mTORC2 activation. The macrophages subtypes differentiation seems to be fundamental in diseases physiopathogenis like chronic kidney disease. Then, we questioned whether M1/M2 polarization in this model could depend on mTORC1 and mTORC2 activation. Moreover, the macrophages subtypes differentiation seems to be fundamental to diseases physiopathogenia as chronic kidney disease (CKD). Thus, in this project, we aim to verify the role of mTOR complexes (mTORC1/2) in M1 and M2 macrophages polarization and verify the activation prevalence of these complexes in chroninc renal injury by inducing the unilateral ureteral obstruction (UUO). This study intend to investigate for the first time the role of mTORC1/2 in M1 and M2 modulation, and also in an unprecedented manner unveil the mechanisms of mTOR complexes in CKD development.
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