15-Deoxy-prostaglandin J(2) inhibits PDGF-A and -B chain expression in human vascular endothelial cells independent of PPAR gamma.
15-Deoxy-prostaglandin J(2)(15d-PGJ(2)) is an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARgamma) and plays an important role in the regulation of endothelial cell growth and apoptosis. However, the detailed mechanisms are poorly understood. We hypothesized that 15d-PGJ(2) might affect PDGF expression in endothelial cells through activating PPARgamma. Here we documented that 15d-PGJ(2) dose-dependently inhibited phorbol-12-myristate-13-acetate (PMA)-stimulated expression of the PDGF-A and PDGF-B chain in human umbilical vein endothelial cells (HUVEC) by Northern blot and Western blot analyses. In contrast, the synthetic and high-affinity PPARgamma agonists, including ciglitazone and GW7845, did not affect PMA-induced PDGF expression. In addition, we found that the PPARgamma antagonist GW9662 did not block the effects of 15d-PGJ(2) on PDGF expression. Furthermore, Northern blot analysis showed that 15d-PGJ(2) inhibited the expression of Sp1, which is a well-known positive regulator of PDGF transcription. Taken together, our results demonstrate that the inhibition of PDGF expression by 15d-PGJ(2) in HUVEC is independent of PPARgamma, but may be through the downregulation of Sp1.
Zhang
Jifeng
J
Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310, USA.
Fu
Mingui
M
Zhao
Luning
L
Chen
Yuqing E
YE
D002478:Cells, Cultured; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000502:physiology*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C075278:platelet-derived growth factor A; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2