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Abstract Details

Altered Expression of microRNA-320 and Its Specific Targets, Transferrin Receptor Protein 1 and Matrix Metallopeptidase 9, in B Cells from Patients with Multiple Sclerosis
MS and Related Diseases
P03 - (-)
238
BACKGROUND: B cells are strongly implicated in the pathogenesis of multiple sclerosis (MS). Certain miRNAs can inhibit the output of specific protein-coding genes implicated in B cell activation and differentiation. The role of miRNA regulation of B cells in MS is not well understood.
DESIGN/METHODS: B cells and monocytes were separated from untreated patients with clinically isolated syndrome, relapsing-remitting MS, and age- and gender-matched control healthy subjects (CHS). Expression of 904 miRNAs was tested by microarrays followed by validation with real-time PCR. Expression of molecules targeted by miRNAs was analyzed by cDNA arrays and Western blot. Transfection experiments with miRNA inhibitors were conducted to prove the inhibitory effect of endogenous miR-320 on expression of its targets.
RESULTS: Relative expression of miR-320 was significantly decreased in patients B cells (0.041 卤 0.0184, n =11) compared to CHS (0.139 卤 0.033, n=8), p = 0.014, but not in monocytes. Relative expression of Matrix metallopeptidase 9 (MMP-9), a protein implicated in disruption of the blood-brain barrier (BBB) and specifically targeted by miR-320, was increased in patients' B cells (0.396卤0.069, n=8) compared to CHS (0.192卤0.040, n=6), p = 0.038. To test whether endogenous miRNA-320 inhibits MMP-9 secretion, B cells from CHS were transfected with a specific miR-320 inhibitor which led to upregulation of MMP-9 secretion to levels seen in MS patients. B cells of patients also had increased expression of Transferrin receptor protein 1 (TFRC), another molecule specifically targeted by miR-320 and promoting cell proliferation.
CONCLUSIONS: miR-320 expression is selectively decreased in B cells of patients with MS. This is associated with increased expression of miR-320-specific targets, TFRC and MMP-9, which promote cell proliferation and BBB disruption, respectively. miR-320 is a potential therapeutic target in MS.
Authors/Disclosures
Latt Latt Aung, MD
PRESENTER 		No disclosure on file
Suhayl S. Dhib-Jalbut, MD, FAAN (Rutgers University) No disclosure on file
Konstantin E. Balashov, MD, PhD, FAAN (Department of Neurology, BMC and BUSM) Dr. Balashov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech.
Vladimir S. Kostic, MD, PhD (Institute of Neurology CCS) Dr. Kostic has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Roche. An immediate family member of Dr. Kostic has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Alkaloid. The institution of Dr. Kostic has received research support from Ministry of 好色先生, Science and Technological Development of Serbia.