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Inhibition of TRAF6 alleviates choroidal neovascularization in vivo.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2018 Sep 18; Vol. 503 (4), pp. 2742-2748. Date of Electronic Publication: 2018 Aug 06. - Publication Year :
- 2018
-
Abstract
- Choroidal neovascularization (CNV) is a type of wet age-related macular degeneration (AMD) which is a major cause of blindness in elder patients. Tumor necrosis factor receptor-associated factor 6 (TRAF6) promotes tumor angiogenesis via upregulating the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). Additionally, TRAF6 facilitates the inflammatory response in macrophages and microglia. Here, using mouse laser-induced CNV model and TRAF6 siRNA, the study shows that TRAF6 is a critical player in CNV. The expression of TRAF6, HIF-1α, and VEGF increased in the model. TFAF6 siRNA intravitreal (IVT) injection inhibited CNV formation, as well as expression of HIF-1α and VEGF, activation of macrophages and microglia. Together, our data suggest that TFAF6 inhibition reduces CNV formation via down-regulating expression of HIF-1α and VEGF and activation of macrophages and microglia, demonstrating the unique advantages of TRAF6 inhibition in the alleviation of AMD.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Choroidal Neovascularization genetics
Choroidal Neovascularization metabolism
Choroidal Neovascularization pathology
Disease Models, Animal
Gene Expression Regulation
Humans
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Lasers
Light Coagulation
Macrophages drug effects
Macrophages metabolism
Macrophages pathology
Mice
Mice, Inbred C57BL
Microglia drug effects
Microglia metabolism
Microglia pathology
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Signal Transduction
TNF Receptor-Associated Factor 6 antagonists & inhibitors
TNF Receptor-Associated Factor 6 metabolism
Vascular Endothelial Growth Factor A metabolism
Angiogenesis Inhibitors pharmacology
Choroidal Neovascularization prevention & control
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Ranibizumab pharmacology
TNF Receptor-Associated Factor 6 genetics
Vascular Endothelial Growth Factor A genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 503
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 30103950
- Full Text :
- https://doi.org/10.1016/j.bbrc.2018.08.034