MMP-9 expression is increased in B lymphocytes during multiple sclerosis exacerbation and is regulated by
Latt Latt Aung1, M Maral Mouradian1, Suhayl Dhib-Jalbut1
1Department of Neurology, Rutgers-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, United States.
Abstract:
B cells are necessary to maintain disease activity in relapsing multiple sclerosis (MS) and produce matrix metallopeptidase-9 (MMP-9), which disrupts the blood-brain barrier. MMP-9 protein expression was increased and expression of microRNA-320a (miR-320a), which targets MMP-9 mRNA, was significantly decreased in B lymphocytes of MS patients during a disease relapse compared to remission. Functional significance of these findings was demonstrated by transfecting human B lymphocytes with miR-320a inhibitor, which led to increased MMP-9 expression and secretion. In summary, expression of miR-320a is decreased in B cells of MS patients and may contribute to increased blood-brain barrier permeability and neurological disability.
Insights
In relapsing multiple sclerosis (MS), decreased microRNA-320a (miR-320a) in B cells elevates matrix metallopeptidase-9 (MMP-9), potentially increasing blood-brain barrier permeability and neurological disability.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Genetics
Background:
- B cells play a critical role in maintaining disease activity in relapsing multiple sclerosis (MS).
- Matrix metallopeptidase-9 (MMP-9) produced by B cells can disrupt the blood-brain barrier.
- MicroRNA-320a (miR-320a) is known to target MMP-9 mRNA.
Purpose of the Study:
- To investigate the expression levels of miR-320a and MMP-9 in B cells of MS patients.
- To determine the functional significance of miR-320a in regulating MMP-9 expression in B cells.
Main Methods:
- Analysis of MMP-9 protein and miR-320a expression in B lymphocytes from MS patients during relapse and remission.
- Functional study involving transfection of human B lymphocytes with a miR-320a inhibitor.
Main Results:
- MMP-9 protein expression was elevated, while miR-320a expression was significantly decreased in B cells of MS patients during relapse compared to remission.
- Inhibition of miR-320a in human B lymphocytes led to increased MMP-9 expression and secretion.
Conclusions:
- miR-320a expression is reduced in B cells of multiple sclerosis patients.
- This downregulation of miR-320a may contribute to increased blood-brain barrier permeability and neurological deficits in MS.
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