RETRACTED ARTICLE: Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction

Abstract

Background Cerebral infarction ranks as the second leading cause of disability and death globally, and inflammatory response of glial cells is the main cause of brain damage during cerebral infarction. Methods Studies have shown that mesenchymal stem cells (MSCs) can secrete exosomes and contribute to cerebral disease. Here, we would explore the function of MSC-derived exosome in cerebral infarction. Results Microarray indicated a decrease of miR-542-3p and an increase of Toll-Like Receptor 4 (TLR4) in middle cerebral artery occlusion (MCAO) mice comparing with sham mice. And luciferase and RIP analysis indicated a binding of miR-542-3p and TLR4. Then, we injected AAV9-miR-542-3p into paracele of sham or MCAO mice. Functional analysis showed that AAV9-miR-542-3p inhibited infarction area and the number of degenerating neurons and suppressed inflammatory factors’ expression and inflammatory cell infiltration. As well, transfection of miR-542-3p mimics into HA1800 cells underwent oxygen and glucose deprivation (OGD). Similarly, overexpression of miR-542-3p alleviated OGD induced cell apoptosis, ROS, and activation of inflammation response. Moreover, miR-542-3p could be packaged into MSCs and secreted into HA1800 cells. The extractive exosome-miR-21-3p treatment relieved MCAO- or OGD-induced cerebral injury and inflammation through targeting TLR4. Conclusion These results confirmed that MSC-derived exosome miR-542-3p prevented ischemia-induced glial cell inflammatory response via inhibiting TLR4. These results suggest possible therapeutic strategies for using exosome delivery of miR-542-3p to cure cerebral ischemic injury.

Identification of an miRNA Regulatory Network and Candidate Markers for Ischemic Stroke Related to Diabetes

“…Weighted gene co-expression network analysis (WGCNA), a method that identifies gene coexpression networks based on topological overlap, 20 was performed on the top 25% of genes explaining the observed expression differences in the GPL6883 and GPL570 platforms. Coexpression network modules were constructed using the WGCNA package in the R suite, 21 as follows.…”

“…Pairwise correlations between genes were used to generate a similarity matrix, then soft threshold power values were calculated to generate a scale-free network topology. The topological overlap matrix (TOM) similarity function 20 was used to convert adjacency values into a TOM matrix, which was used to cluster genes into different modules.…”

“…18,19 In fact, ischemic stroke has been linked to dysregulation of miRNAs, which have been proposed as potential therapeutic strategies. 10,20 The present study aimed to explore molecular mechanisms and potential markers of ischemic stroke in patients with T2DM, based on analysis of differential mRNA and miRNA expression profiles in patients and controls.…”

“… 18 , 19 In fact, ischemic stroke has been linked to dysregulation of miRNAs, which have been proposed as potential therapeutic strategies. 10 , 20 …”

Recent Insight on the Non-coding RNAs in Mesenchymal Stem Cell-Derived Exosomes: Regulatory and Therapeutic Role in Regenerative Medicine and Tissue Engineering

“…Toll-like receptor 4 (TLR4) is a PRR located on the cell surface of microglia and other macrophages and is involved in intracellular signaling via the NF-kB pathway (133). Cai et al (96) showed that decreasing the expression of TLR4 via delivery of miR-542-3p enriched MSC-exosomes to MCAO/R mice reduced infarct volume, edema, and infiltration of inflammatory cells.…”