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Open Access 01-12-2022 | Multiple Sclerosis | Research

MicroRNA-210 regulates the metabolic and inflammatory status of primary human astrocytes

Authors: Nicholas W. Kieran, Rahul Suresh, Marie-France Dorion, Adam MacDonald, Manon Blain, Dingke Wen, Shih-Chieh Fuh, Fari Ryan, Roberto J. Diaz, Jo Anne Stratton, Samuel K. Ludwin, Joshua A. Sonnen, Jack Antel, Luke M. Healy

Published in: Journal of Neuroinflammation | Issue 1/2022

Abstract

Background

Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases in the brain. Astrocyte function is subject to modulation by microRNAs (miRs), which are short nucleotide strands that regulate protein expression in a post-transcriptional manner. Understanding the miR expression profile of astrocytes in disease settings provides insight into the cellular stresses present in the microenvironment and may uncover pathways of therapeutic interest.

Methods

Laser-capture microdissection was used to isolate human astrocytes surrounding stroke lesions and those from neurological control tissue. Astrocytic miR expression profiles were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Primary human fetal astrocytes were cultured under in vitro stress conditions and transfection of a miR mimic was used to better understand how altered levels of miR-210 affect astrocyte function. The astrocytic response to stress was studied using qPCR, enzyme-linked immunosorbent assays (ELISAs), measurement of released lactate, and Seahorse.

Results

Here, we measured miR expression levels in astrocytes around human ischemic stroke lesions and observed differential expression of miR-210 in chronic stroke astrocytes compared to astrocytes from neurological control tissue. We also identified increased expression of miR-210 in mouse white matter tissue around middle cerebral artery occlusion (MCAO) brain lesions. We aimed to understand the role of miR-210 in primary human fetal astrocytes by developing an in vitro assay of hypoxic, metabolic, and inflammatory stresses. A combination of hypoxic and inflammatory stresses was observed to upregulate miR-210 expression. Transfection with miR-210-mimic (210M) increased glycolysis, enhanced lactate export, and promoted an anti-inflammatory transcriptional and translational signature in astrocytes. Additionally, 210M transfection resulted in decreased expression of complement 3 (C3) and semaphorin 5b (Sema5b).

Conclusions

We conclude that miR-210 expression in human astrocytes is modulated in response to ischemic stroke disease and under in vitro stress conditions, supporting a role for miR-210 in the astrocytic response to disease conditions. Further, the anti-inflammatory and pro-glycolytic impact of miR-210 on astrocytes makes it a potential candidate for further research as a neuroprotective agent.

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Title: MicroRNA-210 regulates the metabolic and inflammatory status of primary human astrocytes
Authors: Nicholas W. Kieran
Rahul Suresh
Marie-France Dorion
Adam MacDonald
Manon Blain
Dingke Wen
Shih-Chieh Fuh
Fari Ryan
Roberto J. Diaz
Jo Anne Stratton
Samuel K. Ludwin
Joshua A. Sonnen
Jack Antel
Luke M. Healy
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Multiple Sclerosis
Stroke
Published in: Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-021-02373-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

MicroRNA-210 regulates the metabolic and inflammatory status of primary human astrocytes

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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