Targeted Stage-Specific Inflammatory microRNA Profiling in Urine During Disease Progression in Experimental Autoimmune Encephalomyelitis: Markers of Disease Progression and Drug Response

Singh, Jaspreet; Deshpande, Mandar; Suhail, Hamid; Rattan, Ramandeep; Giri, Shailendra

doi:10.1007/s11481-015-9630-0

ORIGINAL ARTICLE
Published: 16 August 2015

Targeted Stage-Specific Inflammatory microRNA Profiling in Urine During Disease Progression in Experimental Autoimmune Encephalomyelitis: Markers of Disease Progression and Drug Response

Jaspreet Singh¹,
Mandar Deshpande¹,
Hamid Suhail¹,
Ramandeep Rattan¹ &
Shailendra Giri¹

Journal of Neuroimmune Pharmacology volume 11, pages 84–97 (2016)Cite this article

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Abstract

Recently, microRNAs (miRNAs) have been implicated in regulating neuroinflammatory and demyelinative responses in multiple sclerosis (MS) and its mouse model of experimental autoimmune encephalomyelitis (EAE). miRNAs have also been studied as biomarkers of disease pathology and drug-response in MS. However, no complete miRNA profiling at various stages of EAE disease has been examined, especially in the urine. We carried out a systematic analysis of miRNAs in the urine exosomes as well as in the plasma and spinal cord at pre-onset, onset and peak stages of EAE established in the chronic B6 mice model. For the first time, we provide evidence that urine exosomes can be a specific and sensitive source of miRNA biomarkers for all 3 stages of EAE disease. In a significant observation, we observed that miR-155-5p expression increased in urine exosomes, plasma and spinal cord 6 days before the onset of disease, suggesting its early involvement in the pathology of EAE disease. We also analyzed the effect of Glatiramer acetate (GA; copaxone) treatment, an approved treatment for MS patients, in modulating miRNA expression at the peak of EAE disease. We identified miR-155-5p, miR-27a-3p, miR-9-5p and miR-350-5p as putative GA-treatment responsive miRNA biomarkers. Since, EAE is a mainly CD4 cells mediated disease, we also examined the above set of miRNAs and found to be significantly altered in T cells polarized to Th1 and Th17 phenotype, similar to urine exosomes. Thus, urine exosome miRNAs hold the potential to be defined as novel accessible stage-specific biomarkers of EAE (MS) disease as well as treatment response.

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Acknowledgments

The study was supported by Henry Ford hospital internal funding (A20020) and in part by research grant from National Multiple Sclerosis Society (RG 4311A4/4) to SG. The authors thank Stephanie Stebens for editing the manuscript. Mandar Deshpande gave the idea to examine miRNA in urine exosomes of EAE.

Conflict of Interest

Authors declare that they have no conflicts of interest.

Research Involving Animals

All animal protocols were approved by the Institutional Animal Care and Use Committee of the Henry Ford Health System, Detroit, MI.

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Department of Neurology, E&R Building, Room 4051 Henry Ford Health System, Detroit, MI, 48202, USA
Jaspreet Singh, Mandar Deshpande, Hamid Suhail, Ramandeep Rattan & Shailendra Giri

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Jaspreet Singh
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Mandar Deshpande
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Hamid Suhail
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Ramandeep Rattan
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Shailendra Giri
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Correspondence to Shailendra Giri.

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Table S1

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in Urine exosomes at pre-onset stage of EAE (XLS 77 kb)

Table S2

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in plasma exosomes at pre-onset stage of EAE (XLS 77 kb)

Table S3

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in the spinal cord at pre-onset stage of EAE (XLS 83 kb)

Table S4

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in Urine exosomes at onset stage of EAE (XLS 82 kb)

Table S5

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in plasma exosomes at onset stage of EAE (XLS 77 kb)

Table S6

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in the spinal cord at onset stage of EAE (XLS 77 kb)

Table S7

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in Urine exosomes at peak stage of EAE (XLS 77 kb)

Table S8

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in plasma exosomes at peak stage of EAE (XLS 82 kb)

Table S9

miScript miRNA PCRArray dataset for “Inflammatory response and autoimmune” miRNAs in the spinal cord at peak stage of EAE (XLS 84 kb)

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Singh, J., Deshpande, M., Suhail, H. et al. Targeted Stage-Specific Inflammatory microRNA Profiling in Urine During Disease Progression in Experimental Autoimmune Encephalomyelitis: Markers of Disease Progression and Drug Response. J Neuroimmune Pharmacol 11, 84–97 (2016). https://doi.org/10.1007/s11481-015-9630-0

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Received: 08 May 2015
Accepted: 03 August 2015
Published: 16 August 2015
Issue Date: March 2016
DOI: https://doi.org/10.1007/s11481-015-9630-0

Keywords

microRNA
Experimental autoimmune encephalomyelitis
Multiple sclerosis
Copaxone
Biomarker
Urinary exosomes