Friday, 27 January 2012

Research: MicroRNA in Multiple Sclerosis

Paraboschi EM, Soldà G, Gemmati D, Orioli E, Zeri G, Benedetti MD, Salviati A, Barizzone N, Leone M, Duga S, Asselta R. Genetic association and altered gene expression of mir-155 in multiple sclerosis patients.Int J Mol Sci. 2011;12:8695-712.

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system characterized by chronic inflammation, demyelination, and axonal damage. As microRNA (miRNA)-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response, miRNA deregulation may result in defects in immune tolerance.

In this frame, we sought to explore the possible involvement of miRNAs in MS pathogenesis by monitoring the differential expression of 22 immunity-related miRNAs in peripheral blood mononuclear cells of MS patients and healthy controls, by using a microbead-based technology.

Three miRNAs resulted greater than 2 folds up-regulated in MS vs controls, whereas none resulted down-regulated. Interestingly, the most up-regulated miRNA (mir-155; fold change = 3.30; P = 0.013) was previously reported to be up-regulated also in MS brain lesions. Mir-155 up-regulation was confirmed by qPCR experiments. The role of mir-155 in MS susceptibility was also investigated by genotyping four single nucleotide polymorphisms (SNPs) mapping in the mir-155 genomic region. A haplotype of three SNPs, corresponding to a 12-kb region encompassing the last exon of BIC (the B-cell Integration Cluster non-coding RNA, from which mir-155 is processed), resulted associated with the disease status (P = 0.035; OR = 1.36, 95% CI = 1.05-1.77), suggesting that this locus strongly deserves further study.

Recently we introduced you to the concept of microRNA and that they may influence the effects of proteins, Mir 155 has been implicated in controlling the immune response, which is aletered during MS. Animal studies have suggested that Mir55 can promote autoimmune inflammation by enhancing inflammatory T cell development Mice that lack Mir55 develop less MS-like disease than mice that produce Mir155. That Msers have elevated levels of Mir55 may not be a good thing, but it suggests that by inhibiting the development of Mir55 there may be benefit to be had.


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