MicroRNAs in gray and white matter multiple sclerosis lesions: impact on pathophysiology

Teuber‐Hanselmann, Sarah; Meinl, Edgar; Junker, Andreas

doi:10.1002/path.5399

Cited by 22 publications

(13 citation statements)

References 130 publications

(203 reference statements)

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“…In this context, we explored three representative members of the let-7 family (let-7b-5p, let-7e-5p, let-7f-5p) in terms of CSF abundance and correlation with other 21 MS-related miRNAs as well as potential implications in MS disease. Although all let-7 miRNAs have the possibility to control miRNA biogenesis and functioning because they share the same repertoire of target mRNAs with a role in miRNA metabolism, we specifically identified let-7b-5p as a possible hub of a network of seven miRNAs highly linked to MS [54][55][56][57][58][59][60][61][62][63]74]. Neither let-7e-5p or let-7f-5p showed such strong correlations with other detected miR-NAs in the CSF, suggesting that the timing and cellular sources are as important as the target mRNA subset in MS regulation.…”

Section: Discussionmentioning

confidence: 99%

“…More in detail, we observed strong and direct correlations (r > 0.5) between let-7b-5p and miR-451a (r = 0.84), miR-223-3p (r = 0.68), miR-92a-3p (r = 0.63) and miR-16-5p (r = 0.54). Interestingly, all these miRNAs have been implicated in MS as crucial regulators of the immune system [54][55][56][57][58][59] and/or CNS homeostasis [55,[60][61][62][63]. Similar considerations can be made about miRNAs that were milder correlated with let-7b-5p (0.4 < r ≤ 0.5), like miR-24-3p and miR-34a-5p, or with the remyelination-related miR-219-3p [36], suggesting that multiple but common cellular sources participate to their release into the CSF [6,64].…”

Section: Let-7b-5p Is a Possible Regulatory Hub Of The Pattern Of Ms-mentioning

confidence: 99%

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The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Mandolesi

Rizzo

Balletta

et al. 2021

Cells

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The identification of microRNAs in biological fluids for diagnosis and prognosis is receiving great attention in the field of multiple sclerosis (MS) research but it is still in its infancy. In the present study, we observed in a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number of microRNAs implicated in MS, as well as with a variety of inflammation-related protein factors, showing specific expression patterns coherent with let-7b-5p-mediated regulation. Additionally, we found that the CSF let-7b-5p levels were significantly reduced in patients with the progressive MS compared to patients with relapsing-remitting MS and were negatively correlated with characteristic hallmark processes of the two phases of the disease. Indeed, in the non-progressive phase, let-7b-5p inversely associated with both central and peripheral inflammation; whereas, in progressive MS, the CSF levels of let-7b-5p negatively correlated with clinical disability at disease onset and after a follow-up period. Overall, our results uncovered, by the means of a multidisciplinary approach and multiple statistical analyses, a new possible pleiotropic action of let-7b-5p in MS, with potential utility as a biomarker of MS course.

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Section: Discussionmentioning

confidence: 99%

Section: Let-7b-5p Is a Possible Regulatory Hub Of The Pattern Of Ms-mentioning

confidence: 99%

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Mandolesi

Rizzo

Balletta

et al. 2021

Cells

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“…There are fewer studies of miRNAs in MS lesions but these have nevertheless identified miRNAs regulating the resident CNS cells central to MS pathology (Junker et al, 2009;Noorbakhsh et al, 2011;Tripathi et al, 2019;Fritsche et al, 2020). Despite considerable lesion and neurological heterogeneity observed in MS, collated findings suggest that there are conserved miRNA profiles that influence gliosis, inflammation, demyelination and remyelination (Teuber-Hanselmann et al, 2020). Junker et al identified 20 upregulated and 8 downregulated miRNAs in active MS lesions compared to normal appearing white matter (NAWM) (Junker et al, 2009).…”

Section: Microglial Transcriptomics: the Link Between Genotype And Phenotypementioning

confidence: 99%

miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology

2021

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Microglia are the resident immune cells of the central nervous system and important regulators of brain homeostasis. Central to this role is a dynamic phenotypic plasticity that enables microglia to respond to environmental and pathological stimuli. Importantly, different microglial phenotypes can be both beneficial and detrimental to central nervous system health. Chronically activated inflammatory microglia are a hallmark of neurodegeneration, including the autoimmune disease multiple sclerosis (MS). By contrast, microglial phagocytosis of myelin debris is essential for resolving inflammation and promoting remyelination. As such, microglia are being explored as a potential therapeutic target for MS. MicroRNAs (miRNAs) are short non-coding ribonucleic acids that regulate gene expression and act as master regulators of cellular phenotype and function. Dysregulation of certain miRNAs can aberrantly activate and promote specific polarisation states in microglia to modulate their activity in inflammation and neurodegeneration. In addition, miRNA dysregulation is implicated in MS pathogenesis, with circulating biomarkers and lesion specific miRNAs identified as regulators of inflammation and myelination. However, the role of miRNAs in microglia that specifically contribute to MS progression are still largely unknown. miRNAs are being explored as therapeutic agents, providing an opportunity to modulate microglial function in neurodegenerative diseases such as MS. This review will focus firstly on elucidating the complex role of microglia in MS pathogenesis. Secondly, we explore the essential roles of miRNAs in microglial function. Finally, we focus on miRNAs that are implicated in microglial processes that contribute directly to MS pathology, prioritising targets that could inform novel therapeutic approaches to MS.

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“…Ortholog genes share an evolutionary connection and usually present similar roles in different organisms, so some features of an ortholog gene from a particular species can support the understanding of this feature in another specie [28]. Studies demonstrated a correlation between mir186 expression in regulatory processes involved in the development of human disorders, such as hodgkin lymphoma [29], multiple sclerosis [30], hepatocarcinogen [31], and Head and neck squamous cell carcinoma [32].…”

Section: Differentially Expressed Mirnasmentioning

confidence: 99%

mir186 and mir145 In vivo Evaluation and Enrichment in Rats Submitted to Treadmill Strenuous Exercise

Freitas

Pacheco

Felipe

et al. 2021

IJBcRR

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Aims: The present study aimed to identify miRNAs differentially expressed in rats submitted to strenuous exercise and in silico investigation of the biological implication of the findings. Place and Duration of Study: The in vivo experiments and analyses were performed in the Laboratory of Biochemistry and Gene Expression – LABIEX of the Superior Institute of Biomedical Science – ISCB from the State University of Ceará. Between 2017-2020. Methodology: The study was performed using as subjects 2-month-old male wistar rats, which initially were submitted to 2-week adaptation training. Later the animals were separated in two distinct groups, control (C) and trained (T), where only T performed a single session of strenuous exercise, while C were not submitted to this treatment. The applied exercise protocol consisted in a running training in treadmill with speed constant increasing until the animal exhaustion which was measured by the animal refusal to keep running. After 24h, soleus muscle was desiccated and submitted to RNAseq sequencing protocols. Obtained data were statistically evaluated in R environment with EBSeq package, to characterize and predict the miRNAs and their targets were used bioinformatics tools Gene Cards, mi RBase enrichR and KEGG. Results: Two differentially expressed miRNAs were found, mir145 and mir 186, both with downregulated expression pattern in strenuous exercise. These miRNAs have a total of 1201 predicted target genes, 67 were repeated and mostly correlate to cardiovascular disease pathways, between those 5 were differentially expressed as down-regulated. Conclusion: In conclusion, the findings suggest that mir186 and mir145 down-regulation profile mediated by strenuous exercise implicates in the non-alteration of the target genes expression profile, and consequently did not mediate alterations in the pathways they are evolved, which are mainly related to signaling and disorders.

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MicroRNAs in gray and white matter multiple sclerosis lesions: impact on pathophysiology

Cited by 22 publications

References 130 publications

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology

mir186 and mir145 In vivo Evaluation and Enrichment in Rats Submitted to Treadmill Strenuous Exercise

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