MicroRNA-155 Inhibition Activates Wnt/β-catenin Signaling to Restore Th17/Treg Balance and Protect against Acute Ischemic Stroke.

Abstract

Acute ischemic stroke (AIS) is a dangerous neurological disease associated with an imbalance in Th17/Treg cells and abnormal activation of the Wnt/β-catenin signaling pathway. This study aims to investigate whether inhibition of miR-155 can activate the Wnt/β-catenin signaling pathway to improve Th17/Treg imbalance and provide neuroprotective effects against stroke. We employed a multi-level experimental design. Firstly, we analyzed the differential gene expression between the miR-155 antagomir-treated group and the control group using high-throughput sequencing to identify potential target genes. Subsequently, we conducted functional and pathway enrichment analysis of the differentially expressed genes using bioinformatics tools. Next, we performed in vivo animal experiments using a mouse model to validate the impact of miR-155 antagomir treatment on the Wnt/β-catenin signaling pathway and improvement of Th17/Treg cell ratios. Lastly, we conducted in vitro cell experiments to validate our findings further. High-throughput sequencing results showed significant differential expression between the miR-155 antagomir-treated group and the control group (BioProject: PRJNA1152758, SRA IDs: SRR30410532, SRR30410531, SRR30410530 for the disease group; SRR30410529, SRR30410528, SRR30410527 for the control group). Bioinformatics analysis revealed potential target genes associated with the Wnt/β-catenin signaling pathway and Th17/Treg cell imbalance. In vitro experiments demonstrated that miR-155 antagomir treatment significantly activated the Wnt/β-catenin signaling pathway and improved Th17/Treg cell ratios. In vivo, animal experiment results indicated that miR-155 antagomir treatment exhibited significant neuroprotective effects against AIS. This study demonstrates that miR-155 antagomir can improve Th17/Treg cell imbalance by activating the Wnt/β-catenin signaling pathway and exhibiting neuroprotective effects against AIS in a mouse model. These findings provide crucial support for miR-155 as a potential therapeutic strategy for stroke and lay the foundation for further research.Significance Statement This study identifies miR-155 as a pivotal regulator of the Th17/Treg cell balance and Wnt/β-catenin signaling pathway in AIS. By inhibiting miR-155, we demonstrate the potential to enhance neuroprotection and modulate immune responses, offering a promising therapeutic avenue for stroke management. These findings contribute to the growing understanding of molecular mechanisms in stroke and provide a foundation for developing miR-155-targeted therapies.