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Expression of disease‐related miRNAs in white‐matter lesions of progressive multiple sclerosis brains

BACKGROUND: MicroRNA (miRNA) expression in the serum of multiple sclerosis (MS) patients has been correlated with white matter (WM) magnetic resonance imaging (MRI) abnormalities. The expression levels and cellular specificity of the target genes of these miRNAs are unknown in MS brain. OBJECTIVE: T...

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Autores principales: Tripathi, Ajai, Volsko, Christina, Datta, Ushasi, Regev, Keren, Dutta, Ranjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530016/
https://www.ncbi.nlm.nih.gov/pubmed/31139683
http://dx.doi.org/10.1002/acn3.750
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author Tripathi, Ajai
Volsko, Christina
Datta, Ushasi
Regev, Keren
Dutta, Ranjan
author_facet Tripathi, Ajai
Volsko, Christina
Datta, Ushasi
Regev, Keren
Dutta, Ranjan
author_sort Tripathi, Ajai
collection PubMed
description BACKGROUND: MicroRNA (miRNA) expression in the serum of multiple sclerosis (MS) patients has been correlated with white matter (WM) magnetic resonance imaging (MRI) abnormalities. The expression levels and cellular specificity of the target genes of these miRNAs are unknown in MS brain. OBJECTIVE: The aim of this study was to analyze and validate the expression of miRNAs, previously reported as dysregulated in sera of MS patients, in white‐matter lesions (WMLs) of progressive MS brains. METHODS: We performed global miRNA expression profiling analysis in demyelinated WMLs of progressive MS brains (n = 5) and compared the significantly altered miRNAs to previously identified miRNAs from sera of MS patients. Top dysregulated miRNAs common between the two datasets were validated in an independent cohort of MS brains by quantitative PCR (qPCR) and in situ hybridization. RESULTS: Among the miRNAs that were significantly changed in WML tissues, 11 were similar to pathogenic and 12 were common to protective miRNAs previously identified in sera and correlating with WM MRI abnormalities. Importantly, the expression levels of 58% of the protective miRNAs (7 of 12) were decreased in MS lesions compared to surrounding normal‐appearing tissue. Target genes of these miRNAs were also altered in MS lesions and queries of cell‐specific databases identified astrocytes and microglia as the key cellular expressers of these genes in MS brains. CONCLUSIONS: We identified miRNAs that correlate with MRI abnormalities in lesioned tissue from MS brains.
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spelling pubmed-65300162019-05-28 Expression of disease‐related miRNAs in white‐matter lesions of progressive multiple sclerosis brains Tripathi, Ajai Volsko, Christina Datta, Ushasi Regev, Keren Dutta, Ranjan Ann Clin Transl Neurol Research Articles BACKGROUND: MicroRNA (miRNA) expression in the serum of multiple sclerosis (MS) patients has been correlated with white matter (WM) magnetic resonance imaging (MRI) abnormalities. The expression levels and cellular specificity of the target genes of these miRNAs are unknown in MS brain. OBJECTIVE: The aim of this study was to analyze and validate the expression of miRNAs, previously reported as dysregulated in sera of MS patients, in white‐matter lesions (WMLs) of progressive MS brains. METHODS: We performed global miRNA expression profiling analysis in demyelinated WMLs of progressive MS brains (n = 5) and compared the significantly altered miRNAs to previously identified miRNAs from sera of MS patients. Top dysregulated miRNAs common between the two datasets were validated in an independent cohort of MS brains by quantitative PCR (qPCR) and in situ hybridization. RESULTS: Among the miRNAs that were significantly changed in WML tissues, 11 were similar to pathogenic and 12 were common to protective miRNAs previously identified in sera and correlating with WM MRI abnormalities. Importantly, the expression levels of 58% of the protective miRNAs (7 of 12) were decreased in MS lesions compared to surrounding normal‐appearing tissue. Target genes of these miRNAs were also altered in MS lesions and queries of cell‐specific databases identified astrocytes and microglia as the key cellular expressers of these genes in MS brains. CONCLUSIONS: We identified miRNAs that correlate with MRI abnormalities in lesioned tissue from MS brains. John Wiley and Sons Inc. 2019-03-21 /pmc/articles/PMC6530016/ /pubmed/31139683 http://dx.doi.org/10.1002/acn3.750 Text en © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Tripathi, Ajai
Volsko, Christina
Datta, Ushasi
Regev, Keren
Dutta, Ranjan
Expression of disease‐related miRNAs in white‐matter lesions of progressive multiple sclerosis brains
title Expression of disease‐related miRNAs in white‐matter lesions of progressive multiple sclerosis brains
title_full Expression of disease‐related miRNAs in white‐matter lesions of progressive multiple sclerosis brains
title_fullStr Expression of disease‐related miRNAs in white‐matter lesions of progressive multiple sclerosis brains
title_full_unstemmed Expression of disease‐related miRNAs in white‐matter lesions of progressive multiple sclerosis brains
title_short Expression of disease‐related miRNAs in white‐matter lesions of progressive multiple sclerosis brains
title_sort expression of disease‐related mirnas in white‐matter lesions of progressive multiple sclerosis brains
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530016/
https://www.ncbi.nlm.nih.gov/pubmed/31139683
http://dx.doi.org/10.1002/acn3.750
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