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

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.

Myo‐Inositol in Fermented Sugar Matrix Improves Human Macrophage Function

“…[ 77 ] Recently, SMIT1 was found in subset of muscle‐infiltrating auto‐aggressive immune cells, of which most were T‐cells and M1 lineage macrophages of clinically confirmed sporadic inclusion body myositis (IBM) patients. [ 78 ] This study reported that higher expression of SMIT1 followed by HMIT expression and negligible expression of SMIT2 in macrophages suggesting significance of SMIT1 and HMIT.…”

The sodium/myo-inositol co-transporter SLC5A3 promotes non-small cell lung cancer cell growth

“…SLC5A3 is essential for the maintaining and transporting myo-inositol [ 9 , 23 , 24 ]. We found that SLC5A3 silencing by shRNA (shSLC5A3-S1 or shSLC5A3-S2) or SLC5A3 KO induced robust myo-inositol depletion in pCan-1 primary NSCLC cells (Fig.…”

“…Overexpression of SLC5A3 is likely associated with the pathophysiology of Down syndrome [ 8 ]. De Paepe et al ., have proposed that SLC5A3 is a pathological hallmark that is upregulated in sporadic inclusion body myositis (IBM) tissues, which could be linked to the degenerative changes and inflammation of the disease [ 9 ]. Andronic et al, reported that swelling-mediated activation and upregulation of SLC5A3 promoted myo-inositol transport and regulated hypotonic volume in mammalian cells [ 10 ].…”

Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx

“…Mutations of ZC3H12A had recently been verified to be associated with ulcerative colitis recently (47,48). Besides, SLC5A3 (solute carrier family 5 member 3) was proved to be promote inflammatory responses in inclusion body myositis (IBM) (49). Their up-regulation might further reduce the antitumor immune response.…”