Identifying miRNAs in multiple sclerosis gray matter lesions that correlate with atrophy measures

Tripathi, Ajai K.; Pandit, Ishani; Perles, Aaron; Zhou, Yadi; Cheng, Feixiong; Dutta, Ranjan

doi:10.1002/acn3.51365

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…A combined microRNA and mRNA profiling in GM lesions vs NAGM found significantly regulated microRNAs in GM lesions, which target genes of axonal guidance, TGFβ-signaling and FOXO signaling ( 63 ). Out of 27 significantly altered microRNAs, four microRNAs (mir149, mir20a, mir29c, mir25) and their targets (e.g .…”

Section: Resultsmentioning

confidence: 99%

“…Out of 27 significantly altered microRNAs, four microRNAs (mir149, mir20a, mir29c, mir25) and their targets (e.g . HIF1A, VEGFA, TGFBR1, TGFBR2, NFKBIB, FGFR1, TNFSF10, BCL2, MAP2K4, STAT3, MMP2, PTEN, CD44 ) were associated with GM atrophy ( Figure 7 ) ( 63 ). Three of the 27 significantly altered microRNAs were also detected in another GM lesional microarray study (mir181b, mir129-5p, mir1180) ( 64 ).…”

Section: Resultsmentioning

confidence: 99%

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A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis

Elkjaer

Röttger

Baumbach³

et al. 2022

Front. Immunol.

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Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently treated, therapies for progression are scarce and suboptimal, and biomarkers to predict the disease course are insufficient. Cure or preventive measures for MS require knowledge of core pathological events at the site of the tissue damage. Novelties in systems biology have emerged and paved the way for a more fine-grained understanding of key pathological pathways within the CNS, but they have also raised questions still without answers. Here, we systemically review the power of tissue and single-cell/nucleus CNS omics and discuss major gaps of integration into the clinical practice. Systemic search identified 49 transcriptome and 11 proteome studies of the CNS from 1997 till October 2021. Pioneering molecular discoveries indicate that MS affects the whole brain and all resident cell types. Despite inconsistency of results, studies imply increase in transcripts/proteins of semaphorins, heat shock proteins, myelin proteins, apolipoproteins and HLAs. Different lesions are characterized by distinct astrocytic and microglial polarization, altered oligodendrogenesis, and changes in specific neuronal subtypes. In all white matter lesion types, CXCL12, SCD, CD163 are highly expressed, and STAT6- and TGFβ-signaling are increased. In the grey matter lesions, TNF-signaling seems to drive cell death, and especially CUX2-expressing neurons may be susceptible to neurodegeneration. The vast heterogeneity at both cellular and lesional levels may underlie the clinical heterogeneity of MS, and it may be more complex than the current disease phenotyping in the clinical practice. Systems biology has not solved the mystery of MS, but it has discovered multiple molecules and networks potentially contributing to the pathogenesis. However, these results are mostly descriptive; focused functional studies of the molecular changes may open up for a better interpretation. Guidelines for acceptable quality or awareness of results from low quality data, and standardized computational and biological pipelines may help to overcome limited tissue availability and the “snap shot” problem of omics. These may help in identifying core pathological events and point in directions for focus in clinical prevention.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis

Elkjaer

Röttger

Baumbach³

et al. 2022

Front. Immunol.

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“…miRNAs dysregulated in cortical lesions as compared to myelinated gray matter, are involved in axonal guidance, TGFb, and FOXO signaling. Furthermore, miR-20a/25/29c/149 * are associated to gray matter atrophy (301).…”

Section: Inflammatory Activity Vs Progression In Relationship To Agingmentioning

confidence: 99%

Molecular Mechanisms of Immunosenescene and Inflammaging: Relevance to the Immunopathogenesis and Treatment of Multiple Sclerosis

Perdaens

Pesch

2022

Front. Neurol.

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Aging is characterized, amongst other features, by a complex process of cellular senescence involving both innate and adaptive immunity, called immunosenescence and associated to inflammaging, a low-grade chronic inflammation. Both processes fuel each other and partially explain increasing incidence of cancers, infections, age-related autoimmunity, and vascular disease as well as a reduced response to vaccination. Multiple sclerosis (MS) is a lifelong disease, for which considerable progress in disease-modifying therapies (DMTs) and management has improved long-term survival. However, disability progression, increasing with age and disease duration, remains. Neurologists are now involved in caring for elderly MS patients, with increasing comorbidities. Aging of the immune system therefore has relevant implications for MS pathogenesis, response to DMTs and the risks mediated by these treatments. We propose to review current evidence regarding markers and molecular mechanisms of immunosenescence and their relevance to understanding MS pathogenesis. We will focus on age-related changes in the innate and adaptive immune system in MS and other auto-immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. The consequences of these immune changes on MS pathology, in interaction with the intrinsic aging process of central nervous system resident cells will be discussed. Finally, the impact of immunosenescence on disease evolution and on the safety and efficacy of current DMTs will be presented.

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“…These two miRNAs have completely dissimilar sequences, suggesting their distinct roles in biological processes 15 . Their dysregulated expression has been reported in various disease conditions, including cancer, 15 autoimmune disorders, 16 and inflammatory diseases 17,18 . In particular, miR‐149‐3p and miR‐149‐5p have shown promising implications in IBD 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Tissue and serum miR‐149‐3p/5p in hospitalized patients with inflammatory bowel disease: Correlation with disease severity and inflammatory markers

Luo,

Chen

2023

The Kaohsiung J of Med Scie

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This study aimed to investigate the expression levels of tissue and serum miR‐149‐3p and miR‐149‐5p in hospitalized patients with inflammatory bowel disease (IBD). A total of 35 ulcerative colitis (UC) patients, 12 Crohn's disease (CD) patients, and 25 healthy controls were included in the study. The miRNAs expressions were measured in tissue and serum samples using quantitative real‐time polymerase chain reaction (qRT‐PCR). Inflammatory biomarkers were measured, including serum albumin, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6), and fecal calprotectin. MiR‐149‐3p and miR‐149‐5p were significantly decreased in the inflamed areas of both CD and UC patients compared to tissue controls, which was consistent with decreased serum levels in IBD patients compared to healthy controls. When distinguishing UC patients from healthy controls, serum miR‐149‐3p showed 74% sensitivity and 96% specificity, while serum miR‐149‐5p exhibited 63% sensitivity and 96% specificity. In the CD versus healthy control comparison, miR‐149‐3p achieved 100% sensitivity and 96% specificity, while miR‐149‐5p demonstrated 92% sensitivity and 96% specificity. In the UC versus CD comparison, miR‐149‐5p showed 75% sensitivity and 77% specificity, while miR‐149‐3p displayed 67% sensitivity and 80% specificity. Significant correlations were identified between the tissue and serum expression of miR‐149‐3p/5p and disease activity scores, as well as inflammatory biomarkers in both CD and UC patients. Decreased expression of miR‐149‐3p and miR‐149‐5p is associated with disease activity in IBD patients. These miRNAs demonstrate diagnostic potential and may serve as biomarkers for monitoring disease activity in IBD.

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Identifying miRNAs in multiple sclerosis gray matter lesions that correlate with atrophy measures

Cited by 11 publications

References 53 publications

A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis

A Systematic Review of Tissue and Single Cell Transcriptome/Proteome Studies of the Brain in Multiple Sclerosis

Molecular Mechanisms of Immunosenescene and Inflammaging: Relevance to the Immunopathogenesis and Treatment of Multiple Sclerosis

Tissue and serum miR‐149‐3p/5p in hospitalized patients with inflammatory bowel disease: Correlation with disease severity and inflammatory markers

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