miR-30a-5p inhibition promotes interaction of Fas+ endothelial cells and FasL+ microglia to decrease pathological neovascularization and promote physiological angiogenesis
Autor: | Michael I. Dorrell, Carli M Wittgrove, Yoshihiko Usui, Maki Kitano, Edith Aguilar, Martin Friedlander, Amelia Schricker, Susumu Sakimoto, Peter D. Westenskow, Salome Murinello, H. Maura Friedlander, Yoshihiro Wakabayashi |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Microglia Cell growth Angiogenesis Biology Fas receptor Fas ligand Endothelial stem cell Neovascularization 03 medical and health sciences Cellular and Molecular Neuroscience 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Neurology Apoptosis medicine Cancer research medicine.symptom 030217 neurology & neurosurgery |
Zdroj: | Glia. 67:332-344 |
ISSN: | 0894-1491 |
Popis: | Ischemia-induced angiogenesis contributes to various neuronal and retinal diseases, and often results in neurodegeneration and visual impairment. Current treatments involve the use of anti-VEGF agents but are not successful in all cases. In this study we determined that miR-30a-5p is another important mediator of retinal angiogenesis. Using a rodent model of ischemic retinopathy, we show that inhibiting miR-30a-5p reduces neovascularization and promotes tissue repair, through modulation of microglial and endothelial cell cross-talk. miR-30a-5p inhibition results in increased expression of the death receptor Fas and CCL2, to decrease endothelial cell survival and promote microglial migration and phagocytic function in focal regions of ischemic injury. Our data suggest that miR-30a-5p inhibition accelerates tissue repair by enhancing FasL-Fas crosstalk between microglia and endothelial cells, to promote endothelial cell apoptosis and removal of dead endothelial cells. Finally, we found that miR-30a levels were increased in the vitreous of patients with proliferative diabetic retinopathy. Our study identifies a role for miR-30a in the pathogenesis of neovascular retinal disease by modulating microglial and endothelial cell function, and suggests it may be a therapeutic target to treat ischemia-mediated conditions. |
Databáze: | OpenAIRE |
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