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Transcription of the vascular endothelial growth factor gene in macrophages is regulated by liver X receptors
- Source :
- The Journal of biological chemistry. 279(11)
- Publication Year :
- 2003
-
Abstract
- Macrophages are an important source of angiogenic activity in wound healing, cancer, and chronic inflammation. Vascular endothelial growth factor (VEGF), a cytokine produced by macrophages, is a primary inducer of angiogenesis and neovascularization in these contexts. VEGF expression by macrophages is known to be stimulated by low oxygen tension as well as by inflammatory signals. In this study, we provide evidence that Vegfa gene expression is also regulated by activation of liver X receptors (LXRs). VEGF mRNA was induced in response to synthetic LXR agonists in murine and human primary macrophages as well as in murine adipose tissue in vivo. The effects of LXR ligands on VEGF expression were independent of hypoxia-inducible factor HIF-1alpha activation and did not require the previously characterized hypoxia response element in the VEGF promoter. Rather, LXR/retinoid X receptor heterodimers bound directly to a conserved hormone response element (LXRE) in the promoter of the murine and human Vegfa genes. Both LXRalpha and LXRbeta transactivated the VEGF promoter in transient transfection assays. Finally, we show that induction of VEGF expression by inflammatory stimuli was independent of LXRs, because these effects were preserved in LXR null macrophages. These observations identify VEGF as an LXR target gene and point to a previously unrecognized role for LXRs in vascular biology.
- Subjects :
- Transcriptional Activation
Vascular Endothelial Growth Factor A
Transcription, Genetic
Angiogenesis
medicine.medical_treatment
Receptors, Cytoplasmic and Nuclear
Inflammation
Biology
Retinoid X receptor
Ligands
Response Elements
Transfection
Biochemistry
Culture Media, Serum-Free
Cell Line
chemistry.chemical_compound
Mice
medicine
Animals
Humans
RNA, Messenger
Liver X receptor
Hypoxia
Promoter Regions, Genetic
Molecular Biology
Cells, Cultured
Liver X Receptors
Hormone response element
Binding Sites
Reverse Transcriptase Polymerase Chain Reaction
Macrophages
Cell Biology
Hypoxia-Inducible Factor 1, alpha Subunit
Orphan Nuclear Receptors
Vascular endothelial growth factor
DNA-Binding Proteins
Mice, Inbred C57BL
Oxygen
Vascular endothelial growth factor A
Cytokine
chemistry
Adipose Tissue
Gene Expression Regulation
Cancer research
RNA
medicine.symptom
Dimerization
Transcription Factors
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 279
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....49cee6f98785b3da3eb2444b427da59a