The SDF-1/CXCR4 ligand/receptor pair is an important contributor to several types of ocular neovascularization
| Autor: | Katsuji Kiuchi, Shu Kachi, Wei Hong Xiao, Raquel Lima e Silva, Sean F. Hackett, Naw Htee Khu, Maria C. Hatara, Catherine Thut, Jikui Shen, Peter A. Campochiaro, Hideo Akiyama, Thomas Lauer, Yuan Yuan Gong, Sadia Aslam, Katsutoshi Yokoi |
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| Rok vydání: | 2007 |
| Předmět: |
Vascular Endothelial Growth Factor A
Receptors CXCR4 genetic structures Pyridines Bone Marrow Cells Mice Transgenic Biology Retinal Neovascularization Biochemistry CXCR4 Retina Neovascularization chemistry.chemical_compound Mice Ischemia Genetics medicine Animals Humans Corneal Neovascularization Receptor Autocrine signalling Hypoxia Molecular Biology Hypoxia (medical) Antigens Differentiation eye diseases Chemokine CXCL12 Vascular endothelial growth factor Mice Inbred C57BL Platelet Endothelial Cell Adhesion Molecule-1 Choroidal neovascularization medicine.anatomical_structure chemistry Immunology Cancer research Leukocyte Common Antigens sense organs medicine.symptom Oligopeptides Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 21(12) |
| ISSN: | 1530-6860 |
| Popis: | Hypoxia causes increased expression of several proteins that have the potential to promote neovascularization. Vascular endothelial growth factor (VEGF) is up-regulated by hypoxia in the retina and plays a central role in the development of several types of ocular neovascularization, but the effects of other hypoxia-regulated proteins are less clear. Stromal-derived factor-1 (SDF-1) and its receptor, CXCR4, have hypoxia response elements in the promoter regions of their genes and are increased in hypoxic liver and heart. In this study, we found that SDF-1 and CXCR4 are increased in hypoxic retina, with SDF-1 localized in glial cells primarily near the surface of the retina and CXCR4 localized in bone marrow-derived cells. Glial cells also expressed CXCR4, which suggested the possibility of autocrine stimulation, but influx of bone marrow-derived cells is the major source of increased levels of CXCR4. High levels of VEGF in the retina in the absence of hypoxia also increased levels of Cxcr4 and Sdf1 mRNA. CXCR4 antagonists reduced influx of bone marrow-derived cells into ischemic retina and strongly suppressed retinal neovascularization, VEGF-induced subretinal neovascularization, and choroidal neovascularization. These data suggest that SDF-1 and CXCR4 contribute to the involvement of bone marrow-derived cells and collaborate with VEGF in the development of several types of ocular neovascularization. They provide new targets for therapeutic intervention that may help to bolster and supplement effects obtained with VEGF antagonists. |
| Databáze: | OpenAIRE |
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