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Title: Control vascular smooth muscle cell phenotype by transcription factors and by cytokines
Author: Cooper, W. N.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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The phenotype of the vascular smooth muscle cells (VSMC) in atherosclerotic lesions differs from that of the VSMC in the normal arterial wall. The VSMC phenotype is controlled by factors which are only beginning to be defined and these factors will include both transcription factors and cytokines. I have identified a novel number of the POU domain family of transcription factors which have been shown to be important in cell lineage determination. However sequence analysis and RT-PCR suggest that the novel gene is a pseudogene. I have also examined the effect of basic helix-loop-helix (bHLH) transcription factors SRF on expression of smooth muscle expressed genes. VSMC express SRF and the bHLH genes dHAND, Twist and Dermo and I have shown that both dHAND and SRF can activate expression from the SM22α promoter, but that Twist and Dermo cannot. Furthermore dHAND and SRF co-operate to augment expression from the SM22α promoter. I have examined smooth muscle gene expression in mouse models with genetic modification of TGF1β cytokine levels, or signalling pathways. No difference was observed in aortic mRNA expression between wild-type mice and mice expressing a dominant negative TGF1β type II receptor, or mice with a single TGFβ1 allele. However female mice with a single TGFβ1 allele were shown to express lower levels of SM-MHC and SMα-actin proteins than their wild-type litter-mates. Interestingly the mRNA levels of all mice regardless of gender or genotype were similar suggesting that TGFβ1 plays a role in the post transcriptional regulation of a subset of SMC specific genes and this may be overridden by male hormones.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available