Inhibition of microRNA-143-3p Attenuates Cerebral Ischemia/Reperfusion Injury by Targeting FSTL1

MicroRNA (miRNA) miR-143-3p has been reported to participate in the progression of myocardial ischemia/reperfusion (I/R) injury, but its function in cerebral I/R injury remains unclear. Mice were subjected to 60 min of cerebral ischemia followed by different times of reperfusion to construct an I/R injury model in vivo. Human neuroblastoma SH-SY5Y cells were treated with oxygen-glucose deprivation (OGD) for 2 h followed by different times of re-oxygenation to establish I/R injury model in vitro. Neurological deficit was assessed by a five-point score. Infarct volume was detected using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The expression of miR-143-3p was evaluated by qRT-PCR. The expression levels of FSTL1, Bcl-2, Bax and cleaved caspase-3 proteins were detected by western blot. The relationship between miR-143-3p and FSTL1 was explored by luciferase reporter assay. Cell viability was measured by CCK-8 assay. Cell apoptosis was evaluated by TUNEL staining and flow cytometry. MiR-143-3p was significantly upregulated during cerebral I/R injury both in vivo and in vitro. Inhibition of miR-143-3p effectively reduced I/R-induced neurological deficit score and infarct volume in vivo, and enhanced cell viability, while decreased cell apoptosis and LDH release of OGD/R-treated SH-SY5Y cells in vitro. Meanwhile, inhibition of miR-143-3p obviously decreased the expression levels of Bax and cleaved caspase-3, while increased the expression levels of Bcl-2. In addition, these changes induced by miR-143-3p inhibition in vitro was effectively reversed by silencing of FSTL1. Our results demonstrated that inhibition of miR-143-3p protected against cerebral I/R injury through targeting FSTL1.

Automated summary

The study found that miR-143-3p expression is significantly upregulated during cerebral I/R injury, and inhibition of miR-143-3p can protect against neurological deficits, reduce infarct volume, enhance cell viability, and decrease cell apoptosis. This protective effect may be achieved through regulating the expression of FSTL1 protein.