Ligands of peroxisome proliferator-activated receptor-gamma increase the generation of vascular endothelial growth factor in vascular smooth muscle cells and in macrophages.
Peroxisome proliferator-activated receptors-gamma (PPARgamma) are ligand-inducible transcription factors of the nuclear hormone receptor superfamily. We examined the effect of PPARgamma activation on the generation of vascular endothelial growth factor (VEGF), one of the major angiogenic agents. Rat vascular smooth muscle cells (VSMC) and murine macrophages RAW264.7 were incubated for 24 h with PPARgamma activators: prostaglandin J2 and ciglitazone. PPARgamma were expressed in VSMC and RAW cells and their activity was upregulated in the presence of PGJ2 and ciglitazone. Incubation of the cells with PPARgamma activators significantly augmented the release of VEGF protein into the media, both in resting and in IL-1beta- or LPS-stimulated cultures. The higher protein generation was connected with the increased expression of mRNA and transcriptional activation of VEGF promoter. We conclude that the activation of PPARgamma upregulates the generation of VEGF and may be involved in the regulation of angiogenesis.
Jozkowicz
A
A
Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Krakow, Poland. alicia.jozkowicz@akh-wien.ac.at
Dulak
J
J
Piatkowska
E
E
Placha
W
W
Dembinska-Kiec
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D007004:Hypoglycemic Agents; D007375:Interleukin-1; D008024:Ligands; D008070:Lipopolysaccharides; D008222:Lymphokines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2; C039671:ciglitazone