期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 57, 期 6, 页码 2522-2532出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.15-18224
关键词
diabetic retinopathy; Amadori-glycated albumin; miR-124; microglia; Rac1
资金
- National Natural Science Foundation of China [81400405]
- Beijing Natural Science Foundation [7154210]
- China Railway Corporation Research and Development of Science and Technology Project [J2014C011-J]
- Project of Beijing Integrated Traditional and Western Medicine of Beijing Municipal Administration of Traditional Chinese Medicine
PURPOSE. To characterize whether the activation of Rac1 is involved in the inflammatory effects produced by Amadori-glycated albumin (AGA) in retinal microglia and to further explore the pathologic pathways of AGA-induced retinal microglial activation and inflammation via a microRNA-dependent mechanism. METHODS. Primary rat retinal microglia were separated and cultured. The levels of TNF-alpha mRNA and soluble TNF-alpha produced by the retinal microglia in response to AGA were measured with quantitative RT-PCR (qRT-PCR) and ELISA. In addition, the GTPase activity of Rac1 was measured using a Rac activation assay kit. Luciferase reporter assays were used to validate the regulation of a putative target of microRNA-124 (miR-124). RESULTS. Amadori-glycated albumin significantly stimulated the expression of TNF-alpha mRNA and protein in cultured retinal microglial cells in a dose- and time-dependent manner. MicroRNA-124 expression was consistently suppressed by AGA, and the inhibitory effect was controlled by histone deacetylases (HDACs). Amadori-glycated albumin induced an increase in Rac1 activation in a dose- and time-dependent manner. Furthermore, our data indicated that Rac1 activation-mediated reactive oxygen species production stimulates p65 NF-kappa B phosphorylation and induces TNF-alpha release from retinal microglial cells. Finally, we demonstrated that miR-124 directly controls Rac1 expression. CONCLUSIONS. The current study indicated that AGA-induced retinal microglial activation and inflammation occur via a miR-124-dependent mechanism.
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