Original Article Diabetes-Induced Extracellular Matrix Protein Expression Is Mediated by Transcription Coactivator

Increased fibronectin expression is a key feature of dia-betic angiopathy. We have previously shown that nuclear factor-B (NF-B) mediates fibronectin expression in en-dothelial cells and in organs affected by diabetes complica-tions. p300, a transcription coactivator, may regulate NF-B activity via poly(ADP-ribose) polymerase (PARP) activation. Hence, we examined the role of p300 in fi-bronectin expression in diabetes. High glucose induced fibronectin expression in the endothelial cells, which was associated with increased p300, PARP activity, and NF-B activation. This p300 alteration is mediated by mitogen-activated protein kinase and protein kinase C and B. We then used p300 small interfering RNA (siRNA) and showed decreased fibronectin and PARP expression, as well as NF-B activation, in the endothelial cells. Examination o