Let-7a promotes microglia M2 polarization by targeting CKIP-1 following ICH.

Abstract

Microglia polarization plays a crucial role in initiating brain inflammatory injury after intracerebral hemorrhage (ICH). Casein Kinase 2 Interacting Protein 1(CKIP-1) has been identified as a transcriptional molecular to manipulate microglia polarization. MiRNAs regulate gene expression and microglia polarization. In the experiment, CKIP-1 has been predicted as a target gene of let-7a. Let-7a, CKIP-1 and downstream proinflammatory mediator production of ICH mice were analyzed. In addition, inflammation, brain edema, and neurological functions in ICH mice were also assessed. Furthermore, let-7a mimic or inhibitors was administrated to study the potential role to manipulate microglia polarization after ICH. We reported that let-7a levels decreased but CKIP-1 levels increased after ICH. Using a dual-luciferase reporter assay, it was demonstrated that CKIP-1 was the target gene of let-7a. Let-7a overexpression decreased the protein levels of CKIP-1 and inhibition of let-7a increased the protein levels of CKIP-1. In addition, our results indicate that let-7a could inhibit expression of proinflammatory cytokines, reduce brain edema, and improve neurological functions in ICH mice. The study indicated that CKIP-1 was a target gene of let-7a and that let-7a regulated microglia M2 polarization by targeting CKIP-1 following ICH.