Studies on transforming growth factor-B signalling and the regulation of gene expression in macrophages
Salter, Rebecca C.
Transforming growth factor-P (TGF-p) plays a crucial anti-atherogenic role. TGF-p \ud classically signals through the Smad pathway but is known to activate other signalling \ud pathways such as the mitogen-activated protein kinase (MAPK) cascades. Foam cell \ud formation is inhibited by TGF-p through the regulation of expression of genes \ud involved in macrophage cholesterol homeostasis. However, the molecular \ud mechanisms underlying this regulation are yet to be fully elucidated. Studying such \ud mechanisms may lead to identification of novel avenues for treatment of this disease \ud and was therefore the main focus of these studies. TGF-p regulates the stability of \ud atherosclerotic plaques through the regulation of expression of genes encoding \ud proteins involved in the turnover of the extracellular matrix (ECM). The ADAMTS \ud proteases cleave proteoglycans within the ECM and have recently been hypothesised \ud to have roles in atherosclerosis. Cytokine regulation of these proteases and \ud elucidation of the molecular mechanisms behind this regulation may enhance \ud understanding of the roles these proteases play in atherosclerosis with a view to \ud identifying novel avenues for treatment of this disease and was therefore an additional \ud focus of these studies.\ud \ud \ud \ud .
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