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  • Myo-Inositol Transporter SLC5A3 Associates with Degenerative Changes and Inflammation in Sporadic Inclusion Body Myositis.

Myo-Inositol Transporter SLC5A3 Associates with Degenerative Changes and Inflammation in Sporadic Inclusion Body Myositis.

Biomolecules (2020-04-03)
Boel De Paepe, Caroline Merckx, Jana Jarošová, Miryam Cannizzaro, Jan L De Bleecker
ABSTRACT

Myo-inositol exerts many cellular functions, which include osmo-protection, membrane functioning, and secondary messaging. Its Na+/myo-inositol co-transporter SLC5A3 is expressed in muscle tissue and further accumulates in myositis. In this study we focused on the peculiar subgroup of sporadic inclusion body myositis (IBM), in which auto-inflammatory responses and degenerative changes co-exist. A cohort of nine patients was selected with clinically confirmed IBM, in which SLC5A3 protein was immune-localized to the different tissue constituents using immunofluorescence, and expression levels were evaluated using Western blotting. In normal muscle tissue, SLC5A3 expression was restricted to blood vessels and occasional low levels on muscle fiber membranes. In IBM tissues, SLC5A3 staining was markedly increased, with discontinuous staining of the muscle fiber membranes, and accumulation of SLC5A3 near inclusions and on the rims of vacuoles. A subset of muscle-infiltrating auto-aggressive immune cells was SLC5A3 positive, of which most were T-cells and M1 lineage macrophages. We conclude that SLC5A3 is overexpressed in IBM muscle, where it associates with protein aggregation and inflammatory infiltration. Based on our results, functional studies could be initiated to explore the possibilities of therapeutic osmolyte pathway intervention for preventing protein aggregation in muscle cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-SLC5A3 antibody produced in mouse, clone 3A6, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-SLC5A11 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-NCAM Antibody, extracellular, clone ERIC-1, Azide free, clone ERIC-1, Chemicon®, from mouse