MicroRNA-23a-3p promotes the perihematomal edema formation after intracerebral hemorrhage via ZO-1.

OBJECTIVE: To explore the relationship between microRNA-23a-3p expression and perihematomal edema (PHE) in patients with acute intracerebral hemorrhage (ICH) and its underlying mechanism. PATIENTS AND METHODS: Clinical data and blood samples on the 3rd day after ICH onset were collected. Head CT was performed in each subject when admitted. Serum expressions of microRNAs were detected by quantitative real-time PCR (qRT-PCR). The relationship between hematoma volume and perihematomal edema was analyzed by correlation analysis. The direct binding of microRNA-23a-3p and zonula occludens-1 (ZO-1) was verified by luciferase activity assay and Western blot, respectively. Moreover, in vitro experiments were carried out by flow cytometry and CCK-8 assay, respectively.
RESULTS: Serum levels of microRNA-23a-3p and microRNA-130a in ICH patients were remarkably higher than those in the control group, microRNA-26a and microRNA-146a, however, were significantly decreased. A positive correlation was observed between the microRNA-23a-3p expression and the volume of relative perihematomal edema (rPHE) on the 3rd day after ICH (r2=0.3985; p=0.0002). Up-regulation of microRNA-23a-3p significantly decreased ZO-1 expression in hCMEC/D3 cells. Results of luciferase activity assay further indicated that microRNA-23a-3p directly targets the wild-type of ZO-1. In vitro results suggested that microRNA-23a-3p expression markedly affects the proliferation and apoptosis of hCMEC/D3 cells. Similar results were obtained after overexpression or knockdown of ZO-1.
CONCLUSIONS: Up-regulated microRNA-23a-3p in ICH patients promotes the apoptosis of cerebral vascular endothelial cells by down-regulatingZO-1, thus participating in the perihematomal edema formation after intracerebral hematoma.