RETRACTED: MicroRNA-410-3p Binds to TLR2 and Alleviates Myocardial Mitochondrial Dysfunction and Chemokine Production in LPS-Induced Sepsis

Abstract

Mitochondrial dysfunction and chemokine production have been reported to be involved in the pathogenesis of sepsis. Our initial bioinformatics analysis identified differentially expressed TLR2 in sepsis and the upstream regulatory microRNA-410-3p (miR-410-3p). Hence, the current study was performed to characterize the potential mechanism by which miR-410-3p modulates mitochondrial dysfunction and chemokine production in lipopolysaccharide (LPS)-induced mice in vivo and cardiomyocytes in vitro . Next, we identified that miR-410-3p was downregulated, while TLR2 was upregulated in LPS-induced mice and cardiomyocytes. In addition, miR-410-3p was confirmed to target and inhibit the TLR2 expression. Thereafter, gain- or loss-of-function experiments were conducted to investigate the effect of miR-410-3p and TLR2 on mitochondrial function and chemokine production. TLR2 knockdown or miR-410-3p overexpression was found to alleviate mitochondrial membrane damage and mitochondrial swelling, in addition to augmenting the levels of adenosine triphosphate, mitochondrial membrane potential, and the expression levels of CCL7, CCL5, CXCL1, and CXCL9 in vivo and in vitro . In conclusion, miR-410-3p-mediated TLR2 inhibition alleviated mitochondrial dysfunction and reduced chemokine production in LPS-induced experimental sepsis. Therefore, the overexpression of miR-410-3p may represent a potential strategy for the treatment of sepsis-induced myocardial injury.

Clinical Significance of the Serum lncRNA NORAD Expression in Patients with Neonatal Sepsis and Its Association with miR-410-3p

“… 29 , 30 In a previous investigation, the decreased miR-410-3p expression is predictive in the sepsis mice models. 31 Furthermore, our report discovered the levels of miR-410-3p were reduced in the NS group and this trend was reversely associated with the relative expression of NORAD, substantiating NORAD might target miR-410-3p in the regulation of NS development. One of the limitations in our subject was that we did not include healthy patients and compare the expression between healthy controls and NS neonates.…”

MiR-410-3p facilitates Angiotensin II–induced cardiac hypertrophy by targeting Smad7

“…Previously it was disclosed that miR-410-3p acted as a protector in hypoxia-induced cardiomyocyte injury [ 31 ]. In line with this, overexpression of miR-410-3p was also suggested a potential therapy for sepsis-induced myocardial injury [ 18 ]. In spite of that, a recent study, however, showed that miR-410-3p aggravated hypoxia/reoxygenation-induced cardiac injury [ 17 ].…”

“…MicroRNA modulates gene expression via targeting recognition the 3ʹ-untranslated region (3ʹ-UTR) of its downstream gene mRNA [ 27 ]. Previous studies showed that miR-410-3p was critically implicated in multiple human diseases [ 18 , 28–30 ]. As for cardiovascular system, available reports are limited and results seem inconsistent across studies.…”

miR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensis

“…Zuo et al elegantly demonstrated the lower levels of miR-410-3p and increased the predicted target TLR2 in LPS-induced sepsis in mice, where miR-410-3p overexpression mediated TLR2 inhibition, relieving mitochondrial dysfunction and chemokine production [59]. miR-410 mimics also reduced IL6 and TNF levels in LPS-stimulated chondrocytes [60].…”