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  • Title: 15-Deoxy-prostaglandin J(2) inhibits PDGF-A and -B chain expression in human vascular endothelial cells independent of PPAR gamma.
    Author: Zhang J, Fu M, Zhao L, Chen YE.
    Journal: Biochem Biophys Res Commun; 2002 Oct 18; 298(1):128-32. PubMed ID: 12379230.
    Abstract:
    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.
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