Thiazolidinediones, a class of anti-diabetic drugs, inhibit Id2 expression through a PPARgamma-independent pathway in human aortic smooth muscle cells.
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 gamma (PPARgamma) activators, might contribute to the anti-atherosclerotic and anti-hypertensive effects of the PPARgamma. 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 PPARgamma activator, had no inhibitory effect on Id2 gene expression. In addition, PPARgamma antagonist GW9662 did not rescue TZD-induced Id2 repression. Taken together, our data suggest that TZDs repress Id2 expression through a PPARgamma-independent pathway.
Zhu
X
X
Cardiovascular Research Institute, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Lin
Y
Y
Zhang
J
J
Fu
M
M
Mao
Z
Z
Chen
Y E
YE
D000813:Anilides / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002839:Chromans / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051797:Inhibitor of Differentiation Protein 2; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012097:Repressor Proteins; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D000077288:Troglitazone; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D002839:Chromans; D004268:DNA-Binding Proteins; D007004:Hypoglycemic Agents; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D010080:Oxazoles; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C401311:GW 7845; D014443:Tyrosine; D000077288:Troglitazone; C039671:ciglitazone