Thiazolidinediones, a class of anti-diabetic drugs, inhibit Id2 expression through a PPARγ-independent pathway in human aortic smooth muscle cells

Abstract.

Inhibitor of DNA binding (Id2) is a member of the helix-loop-helix family of transcription regulators that is known to play important roles in the proliferation and differentiation of many cell types. Overexpression of Id2 has been reported to result in significant enhancement of vascular smooth muscle cell growth via increased S phase entry. We hypothesized that downregulation of Id2 gene expression by thiazolidinediones (TZDs), a class of anti-diabetic drugs and peroxisome proliferator-activated receptor γ (PPARγ) activators, might contribute to the anti-atherosclerotic and anti-hypertensive effects of the PPARγ. Here we document that TZDs, including troglitazone and ciglitazone, repress Id2 gene expression in a doses- and time-dependent manner. However, GW7845, a high-affinity and non-TZD PPARγ activator, had no inhibitory effect on Id2 gene expression. In addition, PPAR& ggr; antagonist GW9662 did not rescue TZD-induced Id2 repression. Taken together, our data suggest that TZDs repress Id2 expression through a PPARγ-independent pathway.