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Role of Wnt signaling in heart disease

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Resumo:Heart failure has a major social-economic impact in our society. Despite major advances in the understanding of this pathology, the mechanisms of its development, as well as its pathophysiology, remain unclear. Therefore, it is our priority to clarify how extra- and intracellular factors are able to modulate heart function. Several pathways and/or factors had already been associated with different phases of heart failure development namely TGF-β, IGF, calcineurin, several GPCRs, MAPK, Akt and GSK-3. More recently, several studies started shedding some light on a putative role of Wnt signaling in heart failure development. Wnt signaling is a major regulator of cell-fate specification during development, proliferation, survival, migration and adhesion. Several diseases including cancer, diabetes, osteoporosis and psychiatric disorders are the result of deregulation of canonical Wnt signaling, due to either genetic alterations or changes in the levels of its effectors. The role of canonical Wnt signaling in heart development is well established and it has been shown to be biphasic, in the sense that its activation is initially required for the commitment of cells to a cardiac lineage and in its inhibition, cardiogenesis is triggered. In heart failure development, a possible role for Wnt signaling has only recently been reported, yet, its results are contradictory. Nonetheless, it was not addressed a possible role exerted by extracellular modulators and receptors of the Wnt pathway. Because of its role in the development of other diseases, and since its extracellular and membrane effectors are regarded as potential targets of pharmacological intervention in the treatment of such pathologies, it became imperative the understanding of Wnt signaling regulation in heart disease and how these interventions would affect heart function. Taking these facts into account, our first goal was to perform a detailed gene expression analysis of different Wnt ligands, receptors and co-receptors, during heart disease development in a type 1 diabetes mellitus rat model. Since in other contexts, Wnt signaling interacts with other pathways known to present a role in the development of diabetic heart disease, such as PPARs and FOXO proteins, we also checked their expression levels. With this approach we aimed starting to unveil a possible role for Wnt signaling in heart disease development as well as possible interactions with other pathways, known to be important of this pathology.
Autores principais:Oliveira, Vasco Sequeira
Ano:2010
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

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