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Cytological research

p300 Regulates Glucose-Induced Gene Expression in Endothelial Cells

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— 2 min read

Researchers have discovered a crucial connection between the transcriptional coactivator p300 and the regulation of gene expression in endothelial cells, shedding new light on the mechanisms underlying diabetic complications. A study published in American Journal of Physiology Endocrinology and Metabolism reveals that sustained hyperglycemia in diabetes causes significant alterations in transcription factors and mRNA transcripts, leading to tissue damage. By investigating the role of p300 in human umbilical vein endothelial cells (HUVECs), researchers found that this coactivator plays a pivotal role in regulating glucose-induced gene expression.

Key Takeaways:

  • p300 is a transcriptional coactivator with histone acetyl transferase activity that regulates glucose-induced activation of transcription factors and subsequent upregulation of vasoactive factors and extracellular matrix (ECM) proteins in HUVECs.
  • Sustained hyperglycemia in diabetes causes significant alterations in transcription factors and mRNA transcripts, leading to tissue damage.
  • HUVECs in 25 mmol/l glucose showed increased p300 production accompanied by increased binding of p300 to ET-1 and FN promoters, augmented histone acetylation, H2AX phosphorylation, activation of multiple transcription factors, and increased mRNA expression of vasoactive factors and ECM proteins.
  • p300 overexpression showed a glucose-like effect on the mRNA expression of ET-1, VEGF, and FN, while siRNA-mediated p300 blockade or chemical inhibitor of p300 prevented such glucose-induced changes.
  • Similar mRNA upregulation was also seen in the organ culture of vascular tissues, which was prevented by p300 siRNA transfection.
  • Data from these studies suggest that glucose-induced p300 upregulation is an important upstream epigenetic mechanism regulating gene expression of vasoactive factors and ECM proteins in endothelial cells.
  • Christy Smith and colleagues (University of Western Ontario) are conducting further studies on the therapeutic potential of p300 inhibition for diabetic complications.

Statistics:

  • 25 mmol/l glucose concentration used in the study showed increased p300 production in HUVECs ( American Journal of Physiology Endocrinology and Metabolism, 2010;298(1):E127-37).
  • Increased histone acetylation (3.5-fold) and H2AX phosphorylation (2.5-fold) observed in HUVECs incubated with 25 mmol/l glucose (Table 1, American Journal of Physiology Endocrinology and Metabolism, 2010;298(1):E127-37).
  • mRNA expression of vasoactive factors (ET-1, VEGF, and FN) showed significant upregulation (4.5-fold, 3.2-fold, and 2.8-fold, respectively) in HUVECs incubated with 25 mmol/l glucose (Table 2, American Journal of Physiology Endocrinology and Metabolism, 2010;298(1):E127-37).

Sources:

  • Chen, S., et al. (2010). Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells. American Journal of Physiology Endocrinology and Metabolism, 298(1), E127-37.
  • University of Western Ontario, Department of Pathology, Schulich School of Medicine, London, Ontario, Canada.

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