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Ning Dong, Bing Xu, Hong Shi, Yan Lu; miR-124 Regulates Amadori-Glycated Albumin-Induced Retinal Microglial Activation and Inflammation by Targeting Rac1. Invest. Ophthalmol. Vis. Sci. 2016;57(6):2522-2532. doi: 10.1167/iovs.15-18224.
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© ARVO (1962-2015); The Authors (2016-present)
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.
Primary rat retinal microglia were separated and cultured. The levels of TNF-α mRNA and soluble TNF-α 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).
Amadori-glycated albumin significantly stimulated the expression of TNF-α 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-κB phosphorylation and induces TNF-α release from retinal microglial cells. Finally, we demonstrated that miR-124 directly controls Rac1 expression.
The current study indicated that AGA-induced retinal microglial activation and inflammation occur via a miR-124-dependent mechanism.
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