Role of microRNAs As Biomarkers in Sepsis-Associated Encephalopathy

Osca-Verdegal, Rebeca; Beltrán-García, Jesús; Pallardó, Federico V.; García‐Giménez, José Luis

doi:10.1007/s12035-021-02445-3

Cited by 23 publications

(19 citation statements)

References 142 publications

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“…MiRNAs are epigenetic regulators of mRNA that downregulate their expression by binding specific sequences of the 3'-UTR of mRNA (Moore et al 2013). As widely reported, the progression of SAE is closely associated with the abnormal regulation of miRNAs (Osca-Verdegal et al 2021). For example, plasma miR-370-3p was identified as a biomarker of SAE by using a transcriptomic profiling analysis (Visitchanakun et al 2020).…”

Section: Introductionmentioning

confidence: 99%

miR-25-3p ameliorates SAE by targeting the TLR4/NLRP3 axis

2022

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Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis. It has been reported that miR-25-3p is closely related to the development of sepsis. However, the detailed mechanism of miR-25-3p in SAE requires further investigation. Caecum ligation and puncture (CLP) was performed to induce SAE in vivo. LPS stimulation was applied to mimic the in vitro inflammatory model. The expression levels of TLR4 and NLRP3 in the cerebral cortex were evaluated by immunofluorescence. The gene and protein expression levels were determined by qRT-PCR and a western blot analysis. ELISA was used to detect the levels of inflammatory cytokines. The interaction between miR-25-3p and TLR4 was validated by a dual luciferase reporter assay. TLR4 and NLRP3 were highly expressed in the cerebral cortex of SAE mice, while miR-25-3p was expressed at low levels. Activation of the inflammasome, increased release of cytokines and microglial activation were also observed in the SAE mouse model. The overexpression of miR-25-3p inhibited the expression of LPS-induced cytokines and microglial activation. Furthermore, miR-25-3p inhibited TLR4 expression by directly targeting TLR4. The anti-inflammatory effect of miR-25-3p in LPS-induced CHME5 was reversed by TLR4 overexpression. miR-25-3p overexpression attenuated the activation of microglia in SAE by inhibiting the NLRP3/IL-1β/IL-18 axis by directly targeting TLR4, suggesting that miR-25-3p may be a potential target for SAE diagnosis and treatment.

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Section: Introductionmentioning

confidence: 99%

miR-25-3p ameliorates SAE by targeting the TLR4/NLRP3 axis

2022

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“…miRNAs have been proposed as to be good biomarkers because they are stably present in biofluids and biospecimens, including blood, urine, and saliva; this availability enables relatively easy collection and analysis using different methods, such as RNA-seq and qPCR 26 , 27 . Abnormal miRNA expression is correlated with the severity of sepsis and may serve as a potential diagnostic and prognostic biomarker in sepsis 16 , 28 .…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes for adult patients with sepsis via RNA sequencing

Zhang

Wei

et al. 2022

Sci Rep

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To screen out potential prognostic hub genes for adult patients with sepsis via RNA sequencing and construction of a microRNA–mRNA–PPI network and investigate the localization of these hub genes in peripheral blood monocytes. The peripheral blood of 33 subjects was subjected to microRNA and mRNA sequencing using high-throughput sequencing, and differentially expressed genes (DEGs) and differentially expressed microRNAs (DEMs) were identified by bioinformatics. Single-cell transcriptome sequencing (10 × Genomics) was further conducted. Among the samples from 23 adult septic patients and 10 healthy individuals, 20,391 genes and 1633 microRNAs were detected by RNA sequencing. In total, 1114 preliminary DEGs and 76 DEMs were obtained using DESeq2, and 454 DEGs were ultimately distinguished. A microRNA–mRNA–PPI network was constructed based on the DEGs and the top 20 DEMs, which included 10 upregulated and 10 downregulated microRNAs. Furthermore, the hub genes TLR5, FCGR1A, ELANE, GNLY, IL2RB and TGFBR3, which may be associated with the prognosis of sepsis, and their negatively correlated microRNAs, were analysed. The genes TLR5, FCGR1A and ELANE were mainly expressed in macrophages, and the genes GNLY, IL2RB and TGFBR3 were expressed specifically in T cells and natural killer cells. Parallel analysis of mRNAs and microRNAs in patients with sepsis was demonstrated to be feasible using RNA-seq. Potential hub genes and microRNAs that may be related to sepsis prognosis were identified, providing new prospects for sepsis treatment. However, further experiments are needed.

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“…The differences may contribute to age and sexually dimorphic responses to sepsis, and emphasize a need for precision/personalized therapeutics to address post-septic cognitive decline. miRs isolated from blood can provide diagnostic and prognostic information concerning sepsis [102,103] and cognition [26,28]. Furthermore, systemic delivery of miR may protect against sepsis induced brain injury [104].…”

Section: Figure 3 Direction Of Mrna Expression Associated With Increased Mir Expression On Day 1 and Day 4 Post-sepsismentioning

confidence: 99%

Influence of age and sex on microRNA response and recovery in the hippocampus following sepsis

Rani

Barter

Kumar

et al. 2022

Aging

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Sepsis, defined as a dysregulated host immune response to infection, is a common and dangerous clinical syndrome. The excessive host inflammatory response can induce immediate and persistent cognitive decline, which can be worse in older individuals. Sex-specific differences in the outcome of infectious diseases and sepsis appear to favor females. We employed a murine model to examine the influence of age and sex on the brain's microRNA (miR) response following sepsis. Young and old mice of both sexes underwent cecal ligation and puncture (CLP) with daily restraint stress. Expression of hippocampal miR was examined in age-and sex-matched controls at 1 and 4 days post-CLP. Few miR were modified in a similar manner across age or sex and these few miR were generally associated with neuroprotection against inflammation. Similar to previous work examining transcription, young females exhibited a better recovery of the miR profile from day 1 to day 4, relative to young males and old females. For young males and all female groups, the initial response mainly involved a decrease in miR expression. In contrast, old males exhibited only upregulated miR on day 1 and day 4 and many of the miR upregulated on day 1 and day 4 were linked to neurodegeneration, increased neuroinflammation, and cognitive impairment. The results emphasize age and sex differences in epigenetic mechanisms that likely contribute to susceptibility or resilience to cognitive impairment due to sepsis.

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Role of microRNAs As Biomarkers in Sepsis-Associated Encephalopathy

Cited by 23 publications

References 142 publications

miR-25-3p ameliorates SAE by targeting the TLR4/NLRP3 axis

miR-25-3p ameliorates SAE by targeting the TLR4/NLRP3 axis

Identification of hub genes for adult patients with sepsis via RNA sequencing

Influence of age and sex on microRNA response and recovery in the hippocampus following sepsis

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