negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of vascular smooth muscle cell differentiation involved in phenotypic switching. [GO_REF:0000058, GOC:BHF, GOC:BHF_miRNA, GOC:rph, GOC:TermGenie, PMID:25089138]

Negative regulation of vascular associated smooth muscle cell differentiation, a crucial process in phenotypic switching, involves a complex interplay of signaling pathways, transcription factors, and epigenetic modifications. This process is characterized by a transition from a contractile, differentiated state to a synthetic, proliferative state. During this transition, smooth muscle cells (SMCs) lose their characteristic contractile proteins, such as smooth muscle α-actin and myosin, and gain the ability to synthesize extracellular matrix components, including collagen and elastin. This switch is driven by a variety of stimuli, including growth factors, cytokines, and mechanical stress.

One key mechanism of negative regulation is the suppression of the expression of genes involved in SMC differentiation. Transcription factors, such as myocardin and serum response factor (SRF), play a pivotal role in promoting SMC differentiation. Negative regulation can occur through the downregulation of these transcription factors or by the upregulation of their repressors.

Another important aspect is the modulation of signaling pathways. The transforming growth factor-beta (TGF-β) signaling pathway, for example, has been shown to play a significant role in promoting SMC differentiation. Conversely, the activation of the Ras/MAPK pathway, often stimulated by growth factors, has been associated with SMC dedifferentiation.

Epigenetic modifications, such as DNA methylation and histone acetylation, can also influence SMC differentiation. Hypermethylation of the promoters of SMC differentiation genes, for example, has been linked to reduced gene expression and a switch towards a synthetic phenotype.

In summary, negative regulation of vascular associated smooth muscle cell differentiation is a multi-faceted process involving the coordinated suppression of differentiation-promoting genes, activation of dedifferentiation pathways, and the modulation of epigenetic marks. These processes contribute to the phenotypic switching of SMCs, playing a critical role in vascular remodeling, atherosclerosis, and other vascular diseases.'
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Proteins (1)

Compounds (21)