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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Collectively, these data suggest that baicalein inhibits AGA-induced MCP-1 expression in retinal ganglion cells via a microRNA-124-dependent mechanism.
Department of Ophthalmology Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.
Ning
N
Dong
Department of Ophthalmology Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.
Bing
B
Xu
Department of Ophthalmology Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.
Hong
H
Shi
Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin, People's Republic of China.
Xin
X
Tang
D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology*; D035683:MicroRNAs / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000418:Albumins; D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D044950:Flavanones; C548144:MIRN124 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; C006680:baicalein