Abstract

Vascular smooth muscle cell (VSMC) differentiation is an essential component of vascular development. Vascular smooth muscle cells do not terminally differentiate, the regulatory factors modulate their phenotype between proliferative and differentiated states, which is a major factor contributing to vascular diseases like atherosclerosis, aneurysms, hypertension, etc. Transforming growth factor β (TGF-β) family is highly conserved in mammals and plays an essential role in VSMC differentiation. The canonical TGF-β pathway is propagated by phosphorylation of receptor-associated Smad proteins (R-Smads) following TGF-β stimulation.Bromodomain-containing protein 4 (BRD4) is a protein encoded by the BRD4 gene in humans. BRD4 is novel epigenetic modulator that has been implicated in different human diseases. It has gained wide attention in the field of cancer and lung diseases due to its multiple roles in the regulation of genes that are important for disease progression. There is increasing evidence that BRD4 also plays a significant role in a variety of cardiovascular diseases, proposing that understanding the mechanisms of BRD4 in these diseases is important for novel target development and clinical treatment. In this proposed study, the novel role and mechanisms of BRD4 in SMC differentiation is being investigated. In the process it was found that 10 T ½ cells successfully induce SMC differentiation, knockdown of BRD4 inhibit markers alpha-SMA and SM22alpha, qPCR showed knockdown by JQ1 and BRD4 does not influence smad phosphorylation (classic pathway). A combination of TAZ and Smad protein was tested .

Date of publication

Summer 8-2024

Document Type

Thesis

Language

english

Persistent identifier

http://hdl.handle.net/10950/4754

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