In summary, our data provide a novel mechanism of transcriptional regulation of fibronectin through CREB that may be used as therapeutic approach to prevent diabetes complications.
We have previously shown that nuclear factor-kappaB (NF-kappaB) mediates fibronectin expression in endothelial cells and in organs affected by diabetes complications. p300, a transcription coactivator, may regulate NF-kappaB activity via poly(ADP-ribose) polymerase (PARP) activation.
These studies show that glucose-induced and ET-mediated FN and ED-B FN expressions involve complex interplays between signaling pathways and that ET may represent an ideal target for therapy in chronic diabetic complications.