Abstract
BackgroundSpinal cord ischemia-reperfusion injury (SCIRI) often leads to neurological damage and mortality. In this regard, understanding the pathology of SCIRI and preventing its development are of great clinic value.MethodsHerein, we analyzed the role of bone marrow mesenchymal stem cell (BMMSC)-derived exosomal microRNA (miR)-124-3p in SCIRI. A SCIRI rat model was established, and the expression of Ern1 and M2 macrophage polarization markers (Arg1, Ym1, and Fizz) was determined using immunohistochemistry, immunofluorescence assay, RT-qPCR, and western blot analysis. Targeting relationship between miR-124-3p and Ern1 was predicted using bioinformatic analysis and verified by dual-luciferase reporter assay. Macrophages were co-cultured with miR-124-3p-containing BMMSC-derived exosomes. M2 macrophages were identified using flow cytometry, and the expression of Arg1, Ym1, and Fizz was determined. In addition, SCIRI rats were injected with miR-124-3p-containing exosomes, spinal cord cell apoptosis was observed using TUNEL assay, and the pathological condition was evaluated with H&E staining.ResultsIn SCIRI, Ern1 was highly expressed and M2 polarization markers were poorly expressed. Silencing Ern1 led to elevated expression of M2 polarization markers. MiR-124-3p targeted and negatively regulated Ern1. Exosomal miR-124-3p enhanced M2 polarization. Highly expressed exosomal miR-124-3p impeded cell apoptosis and attenuated SCIRI-induced tissue impairment and nerve injury. miR-124-3p from BMMSC-derived exosomes ameliorated SCIRI and its associated nerve injury through inhibiting Ern1 and promoting M2 polarization.ConclusionIn summary, exosomal miR-124-3p derived from BMMSCs attenuated nerve injury induced by SCIRI by regulating Ern1 and M2 macrophage polarization.
Highlights
Spinal cord ischemia-reperfusion injury (SCIRI) often leads to neurological damage and mortality
Expression of Endoplasmic reticulum to nucleus signaling 1 (Ern1) as well as M2 macrophage polarization markers including Arg1, Ym1, and Fizz in SCIRI rats was detected by RT-qPCR (Fig. 1a)
The expression of Ern1, Arg1, Ym1, and Fizz was determined by western blot analysis (Fig. 1b), showing that in contrast to normal rats, the protein level of Ern1 was significantly increased, while the protein levels of Arg1, Fizz, and Ym1 were decreased in SCIRI rats (p < 0.05)
Summary
Spinal cord ischemia-reperfusion injury (SCIRI) often leads to neurological damage and mortality. In this regard, understanding the pathology of SCIRI and preventing its development are of great clinic value. Spinal cord ischemia-reperfusion injury (SCIRI) often results from a blockade of the aorta for a certain period occurring during spinal operation or aortic aneurysm surgery and may eventually induce paralysis or paraplegia and neural dysfunction, which can cause great damage to individuals both physically and mentally [1]. Bone marrow mesenchymal stem cell (BMMSC) transplantation is one of the most promising therapies for SCIRI due to BMMSC-derived exosomes [2]. Mesenchymal stem cell (MSC)-derived exosomes are known to function as cellular regulators by transporting proteins, lipids, and RNAs [3]. The function of BMMSC-derived exosomes in SCIRI needs to be explored further
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