Abstract
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.
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Data Availability
The data that support the findings of this study are available on request from the corresponding author: * Zhenguo Liu, Intensive Care Unit, Shaanxi Provincial People’s Hospital, No. 256 Friendship (Youyi) West Road, Xi’an City, Shaanxi Province, 710068, PR. China. The data are not publicly available due to their containing information that could compromise the privacy of research participants.
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Shunda Wang, Zhenguo Liu: study concepts, literature research, clinical studies, data analysis, experimental studies, manuscript writing and review, study design, literature research, experimental studies and manuscript editing, definition of intellectual content, clinical studies, data acquisition and statistical analysis.
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Wang, S., Liu, Z. Inhibition of microRNA-143-3p Attenuates Cerebral Ischemia/Reperfusion Injury by Targeting FSTL1. Neuromol Med 23, 500–510 (2021). https://doi.org/10.1007/s12017-021-08650-6
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DOI: https://doi.org/10.1007/s12017-021-08650-6