miR-30a-5p inhibition promotes interaction of Fas
Animals
Animals, Newborn
Apoptosis
/ drug effects
Cell Line, Transformed
Cell Proliferation
/ drug effects
Chemokine CCL2
/ genetics
Disease Models, Animal
Endothelial Cells
/ drug effects
Gene Expression Regulation
/ drug effects
Humans
Lectins
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
MicroRNAs
/ genetics
Microglia
/ metabolism
Neovascularization, Pathologic
/ drug therapy
Neovascularization, Physiologic
/ drug effects
RNA Interference
/ physiology
RNA, Messenger
/ metabolism
fas Receptor
/ metabolism
CCL2
angiogenesis
ischemia
miR-30a-5p
microglia
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
22
03
2018
revised:
05
09
2018
accepted:
05
09
2018
pubmed:
30
11
2018
medline:
14
5
2019
entrez:
29
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30484883
doi: 10.1002/glia.23543
pmc: PMC6349526
mid: NIHMS992865
doi:
Substances chimiques
Ccl2 protein, mouse
0
Chemokine CCL2
0
Fas protein, mouse
0
Lectins
0
MIRN30a microRNA, mouse
0
MicroRNAs
0
RNA, Messenger
0
fas Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
332-344Subventions
Organisme : NIH HHS
ID : EY11254
Pays : United States
Organisme : NIH HHS
ID : EY022025
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY011254
Pays : United States
Organisme : NEI NIH HHS
ID : R24 EY022025
Pays : United States
Organisme : NIH HHS
ID : R24
Pays : United States
Informations de copyright
© 2018 Wiley Periodicals, Inc.
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