Regulation of the vascular smooth muscle cell phenotype
Abstract: Smooth muscle cells (SMC) are present in many internal organs such as the blood vessels and the gastrointestinal channel. Their main functions are to provide stability to the tissue and to provide contractile capability. SMC are not terminally differentiated but can switch between several phenotypes, which is also known as phenotypic modulation. Unfavourable SMC phenotypes have been proposed to contribute to pathological processes such as atherosclerosis and asthma. The focus of this thesis has been to further elucidate the mechanisms that regulate gene expression in vascular SMC (VSMC).We developed a vascular differentiation system based on mouse embryonic stem cells and confirmed differentiation of VSMC as shown by expression of several marker genes. Moreover, VSMC markers and SMC markers were independently regulated in this system, which correlated with absence of CArG boxes in VSMC gene promoters. We could finally show that PDGF-B and TGF
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