Contributions
Abstract: P462
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Introduction: Micro RNAs (miRNAs) are single stranded, 19-23 nucleotide long, non-coding RNAs that regulate gene expression at posttranscriptional level by complementary binding to 3' untranslated region (UTR) regions of target genes. Modulation of gene expression by miRNAs plays central role in several neurodegenerative diseases including multiple sclerosis (MS), a chronic inflammatory demyelinating disease. Failure in remyelination is considered one of the main reasons for MS disease progression. This failure in remyelination is however commonly associated with presence of immature oligodendrocytes (OLs) within lesions of MS brains.
Objective: To evaluate functional role of miR-27a during oligodendrocyte lineage development.
Methods: Global genome expression analysis and RT-qPCR was applied to analyze and validate miRNA expression level in chronic demyelinated postmortem human brain. Further, role of miR-27a in myelination was investigate using in vitro primary oligodendrocyte progenitor cell (OPCs) culture system.
Results: miR-27a expression was significantly downregulated in demyelinated MS lesion. Our in vitro functional assay showed that transient transfection of chemically synthesized miR-27a (mimic) in OPCs inhibited differentiation of OPCs into mature OLs. We also found that miR-27a overexpression cause significant increase in levels of Chondroitin sulfate proteoglycan 4 (Cspg4/Ng2) protein without increase in proliferation of the OPCs. At mRNA transcripts and protein level, expression of miR-27a showed dysregulation of genes involved in Wnt-β-catenin signaling pathways which have been reported to negatively regulate OLs differentiation.
Conclusions: Taken together, our results indicate that miR-27a may play a major role in arresting OPCs in the immature state leading to remyelination failure in MS.
Disclosure: Conflict of Interest: None
Funding: National Multiple Sclerosis Society USA, (5298) and National Institiute of Health USA, R01 NS096148
Abstract: P462
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Introduction: Micro RNAs (miRNAs) are single stranded, 19-23 nucleotide long, non-coding RNAs that regulate gene expression at posttranscriptional level by complementary binding to 3' untranslated region (UTR) regions of target genes. Modulation of gene expression by miRNAs plays central role in several neurodegenerative diseases including multiple sclerosis (MS), a chronic inflammatory demyelinating disease. Failure in remyelination is considered one of the main reasons for MS disease progression. This failure in remyelination is however commonly associated with presence of immature oligodendrocytes (OLs) within lesions of MS brains.
Objective: To evaluate functional role of miR-27a during oligodendrocyte lineage development.
Methods: Global genome expression analysis and RT-qPCR was applied to analyze and validate miRNA expression level in chronic demyelinated postmortem human brain. Further, role of miR-27a in myelination was investigate using in vitro primary oligodendrocyte progenitor cell (OPCs) culture system.
Results: miR-27a expression was significantly downregulated in demyelinated MS lesion. Our in vitro functional assay showed that transient transfection of chemically synthesized miR-27a (mimic) in OPCs inhibited differentiation of OPCs into mature OLs. We also found that miR-27a overexpression cause significant increase in levels of Chondroitin sulfate proteoglycan 4 (Cspg4/Ng2) protein without increase in proliferation of the OPCs. At mRNA transcripts and protein level, expression of miR-27a showed dysregulation of genes involved in Wnt-β-catenin signaling pathways which have been reported to negatively regulate OLs differentiation.
Conclusions: Taken together, our results indicate that miR-27a may play a major role in arresting OPCs in the immature state leading to remyelination failure in MS.
Disclosure: Conflict of Interest: None
Funding: National Multiple Sclerosis Society USA, (5298) and National Institiute of Health USA, R01 NS096148