Metformin shows anti-inflammatory effects in murine macrophages through Dicer/microribonucleic acid-34a-5p and microribonucleic acid-125b-5p
Abstract
AIMS/INTRODUCTION: Metformin, a widely prescribed antidiabetic agent, has been shown to exhibit anti-inflammatory effects in obese and type 2 diabetes patients, but the mechanism is not well elucidated. Microribonucleic acids (miRNAs) are a group of small non-coding ribonucleic acids that participate in many biological and pathological processes. The aim of the present study was to investigate whether Dicer, a key miRNA biogenesis enzyme, and miRNAs in macrophages are implicated in the anti-inflammatory effects of metformin.
MATERIALS AND METHODS: Enzyme-linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were carried out to verify the anti-inflammatory effects of metformin. miRNA microarray was applied to detect the expression profile of miRNA. Western-blotting, enzyme-linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were used to examine the role Dicer and miRNAs play in the anti-inflammatory effects of metformin.
RESULTS: In parallel with the suppression of interleukin-6 and tumor necrosis factor-α production in resting and lipopolysaccharide-stimulated macrophages, metformin could induce an increase in Dicer and most miRNAs. When Dicer was knocked down, the anti-inflammatory effects of metformin were significantly attenuated. Additionally, the upregulation of miRNA (miR)-34a-5p and miR-125b-5p by metformin were also blunted in Dicer knockdown macrophages. Furthermore, inhibition of…
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