Baicalein Inhibits Amadori-Glycated Albumin-Induced MCP-1 Expression in Retinal Ganglion Cells via a MicroRNA-124-Dependent Mechanism.

Abstract

The purpose of this study was to characterize the inflammatory effect of amadori-glycated albumin (AGA) in cultured rat retinal ganglion cells (RGCs) and to further explore the potential mechanism of the anti-inflammatory effects of baicalein. Primary rat retinal neurons were separated and cultured. The levels of monocyte chemotactic protein-1 (MCP-1) mRNA and soluble MCP-1 produced by RGCs in response to AGA were measured with quantitative reverse transcription-PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the expression of microRNA-124 (miR-124) and histone deacetylases (HDACs) were detected in cultured rat RGCs by qRT-PCR in the presence or absence of baicalein. Luciferase reporter assays were used to validate the regulation of a putative target of miR-124. Amadori-glycated albumin stimulation increased the expression of MCP-1 and inhibited the expression of miR-124 in cultured rat RGCs. In addition, miR-124 directly controlled MCP-1 expression by binding directly to 3'-untranslated region (3'-UTR) of MCP-1. Next, we demonstrated that miR-124 expression was suppressed by HDACs and that treatment of RGCs with HDACs inhibitors increased miR-124 expression and decreased MCP-1 production. Furthermore, application of baicalein in RGCs attenuated AGA-induced MCP-1 expression and upregulated expression of miR-124 by controlling HDAC4 and HDAC5. Collectively, these data suggest that baicalein inhibits AGA-induced MCP-1 expression in retinal ganglion cells via a microRNA-124-dependent mechanism.