Acupuncture Upregulates hsa-miR-550a-3-5p Targeting PECAM1 To Reduce Transendothelial Migration of Inflammatory Cells and Alleviate Migraine.

BACKGROUND

Migraine is a complex neurological disorder. While acupuncture is effective in alleviating migraines, its molecular mechanisms remain unclear. This study aims to explore these mechanisms.

METHODS

We used bioinformatics to identify differentially expressed microRNAs (miRNAs) in migraine patients after acupuncture. Subsequently, luciferase reporter assays were utilized to verify the interaction between miRNAs and their regulated target gene mRNAs. RT-qPCR and Western blot analyzed key miRNAs' regulatory effects on target genes. We also employed Transwell migration assays and a nitroglycerin (NTG)-induced migraine mouse model to systematically evaluate acupuncture's efficacy and mechanism.

RESULTS

Bioinformatics analysis revealed a significant upregulation of Hsa-miR-550a-3-5p in the peripheral blood of migraine patients after acupuncture treatment. Hsa-miR-550a-3-5p could directly inhibit the mRNA and protein expression of platelet and endothelial cell adhesion molecule 1 (PECAM1), reducing nitroglycerin-induced human brain microvascular endothelial cells (HBMECs). Following the downregulation of PECAM1 by hsa-miR-550a-3-5p, the transendothelial migration capacity of monocytes-macrophages was significantly reduced, and reducing the secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Furthermore, it alleviates inflammation by regulating M2 macrophage polarization. In NTG-induced mice, acupuncture relieved migraine-like behaviors, an effect abolished by a miR-550a-3-5p inhibitor.

CONCLUSION

This study is the first to reveal that after acupuncture treatment, hsa-miR-550a-3-5p can be upregulated to target and inhibit PECAM1, reducing the transendothelial migration of inflammatory cells and the release of inflammatory cytokines, thereby alleviating migraine symptoms. This discovery provides scientific evidence for the efficacy of acupuncture and offers a new target for developing miRNA-based precision treatment strategies.