| Background: The Reg signaling pathway is well known to promote proliferation, differentiation and/or to protect cells from apoptosis (programmed cell death) in various organs, such as the pancreas, neuronal tissue, gastrointestinal tract, and skeletal muscle. Heart diseases are one of the major causes of adult and childhood mortality. Cardiac tissue is composed of three main types of cells: cardiomyocytes, vascular cells and cardiac fibroblasts. A loss of cardiomyocytes can lead to heart failure or improper development during embryogenesis, causing congenital heart malformations. Current therapeutic approaches are hindered by the limited regenerative capacity of postnatal cardiomyocytes.;Motivation: The aim of this thesis is to assess the role of the Reg signaling pathway in cardiac tissue by studying its up- and down-regulation, as well as its potential anti-apoptotic effect using HL1 cells, a mouse cardiomyocyte cell line.;Results: This study provides evidence that two REGs are expressed at the gene level in mouse cardiac tissue, mReg1 and mReg3β. These candidates are upregulated and stimulated using a combination of interleukine 6 (IL6) and dexamethasone. Dexamethasone alone also leads to significant increase in the gene expression levels of these Regs and their nuclear targets. mExtl3, a known Reg surface receptor is shown to be expressed in mouse cardiac tissue for the first time, but is not upregulated by the stimulation. When the cells in culture are incubated with recombinant mouse REG1 or REG3β proteins, significant anti-apoptotic response is observed in ethanol-induced apoptosis condition, particularly with mReg3β. Neither the stimulation of Reg signaling pathway using IL6 and dexamethasone nor the addition of recombinant mouse Reg proteins shows an impact on cell proliferation. These findings lead the study to draw conclusions about the anti-apoptotic response and/or protection of the stimulated Reg pathway in the heart, which could be a major breakthrough for regenerative cardiac medicine.;Keywords: mouse cardiac tissue, Reg, Regenerating protein, Extl3, Fas, Fas Ligand, apoptosis, cardiac regeneration. |
