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Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
MicroRNA-7188-5p and miR-7235 regulates Multiple sclerosis in an experimental mouse model
Hairul-Islam Mohamed Ibrahim1, Abdullah AlZahrani2, Hamza Hanieh3
1Biological Sciences Department, College of Science, King Faisal University, Hofouf, Alhasa, 31982, Saudi Arabia; Pondicherry Centre for Biological Science and Educational Trust, Pondicherry, 605005, India.
Abstract:
The short non-coding microRNAs (miRNAs) have emerged as reliable modulators of various pathological conditions including autoimmune diseases in mammals. The current study, aims to identify new potential differential expressed miRNAs and their downstream mRNA targets of the autoimmune disease, Multiple sclerosis (MS). The study identifies a new set of miRNA(s) that are probably implicated in MS using computational tools. The study further carried-out different in vivo and in vitro experiments to check these identified miRNAs could be role in as therapeutic and prognostic applications. Preliminary insilico screening revealed that miR-659-3p, miR-659-5p, miR-684, miR-3607-3p, miR-3607-5p, miR-3682-3p, miR-3682-5p miR-4647, miR-7188-3p, miR-7188-5p and miR-7235 are specifically elevated in the secondary lymphoid cells of EAE mice. In addition, expression of the downstream target mRNA of these miRNAs such as FXBO33, SGMS-1, ZDHHC-9, GABRA-3, NRXN-2 were reciprocal to miRNA expression in lymphoid cells. These confirmed by applying the mimic and silencing miRNA models, suggesting new inflammatory target genes of these promising miRNA markers. The in vivo adoptive transfer model revealed that the suppression of miRNA-7188-5p and miR-7235 changed the pattern of astrocytes and CNS pathophysiology. The current study opens a new miRNA and their mRNA targets in MS disease. The absence of miRNA-7188-5p and miR-7235 enhanced the disease alleviation, confirms the regulatory effect of these targets. These optimized results highlights new set of miRNA's with therapeutic potential in experimental MS. Further studies are required to confirm these miRNA as therapeutic biomarker.
Insights
Researchers identified novel microRNAs (miRNAs) and their mRNA targets implicated in Multiple Sclerosis (MS). Specific miRNAs, like miR-7188-5p and miR-7235, showed therapeutic potential by alleviating disease symptoms in experimental models.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and are implicated in various pathological conditions, including autoimmune diseases.
- Multiple Sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, with complex underlying molecular mechanisms that are not fully understood.
Purpose of the Study:
- To identify novel differentially expressed miRNAs and their downstream mRNA targets in Multiple Sclerosis (MS).
- To investigate the potential therapeutic and prognostic applications of identified miRNAs in MS.
Main Methods:
- Computational tools were used for preliminary in silico screening to identify differentially expressed miRNAs in EAE mice models.
- In vivo and in vitro experiments, including mimic and silencing miRNA models, were conducted to validate miRNA targets and their roles.
- Adoptive transfer models were employed to assess the in vivo effects of specific miRNAs on disease progression and central nervous system (CNS) pathophysiology.
Main Results:
- A set of miRNAs, including miR-659-3p, miR-659-5p, miR-684, miR-3607, miR-3682, miR-4647, miR-7188, and miR-7235, were found to be elevated in the secondary lymphoid cells of EAE mice.
- Reciprocal expression patterns were observed between these miRNAs and their downstream target mRNAs (e.g., FXBO33, SGMS-1, ZDHHC-9, GABRA-3, NRXN-2) in lymphoid cells.
- Suppression of miR-7188-5p and miR-7235 in vivo altered astrocyte patterns and CNS pathophysiology, leading to enhanced disease alleviation in experimental MS models.
Conclusions:
- The study identified a novel set of miRNAs and their mRNA targets implicated in the pathogenesis of MS.
- Specific miRNAs, particularly miR-7188-5p and miR-7235, demonstrate significant therapeutic potential for experimental MS.
- These findings highlight promising miRNA biomarkers for therapeutic intervention and further research in MS.

