The MiR-139-5p and CXCR4 axis may play a role in high glucose-induced inflammation by regulating monocyte migration.

MicroRNAs, a class of small non-coding RNA molecules that regulate gene expression post-transcriptionally, are implicated in various pathological conditions including diabetes mellitus (DM). DM has been increasingly recognized as an inflammatory disease and monocytes play a key role in propagating inflammation under hyperglycemic conditions. We hypothesize that high glucose dysregulates microRNAs to promote monocyte inflammatory activity, which may contribute to the pathogenesis of DM. THP-1 monocytes were cultured in normal (5 mM) and high (25 mM) glucose conditions. RT-qPCR and Western blotting were performed to assay microRNAs and proteins, respectively. Monocytes were transfected with microRNA mimics using Lipofectamine RNAiMAX reagent. THP-1 monocyte growth was assessed using Calcein-AM dye and a Boyden chamber assay was applied to measure monocyte migration. The results showed that high glucose downregulated miR-139-5p associated with increased protein expression of CXCR4, an experimentally validated target of miR-139-5p. Correspondingly, treatment with high glucose resulted in a significant increase in THP-1 cell migration towards SDF-1, a cognate ligand for CXCR4. MiR-139-5p overexpression inhibited high glucose-induced CXCR4 expression, leading to reduced cell migration towards SDF-1. High glucose did not affect THP-1 monocyte growth. In conclusion, the miR-139-5p-CXCR4 axis may play a role in high glucose-induced inflammation by regulating monocyte migration.