Department of Neurology; Laboratory for Neuropathology, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
Biomolecules. 2020 Mar 30;10(4):521. doi: 10.3390/biom10040521.
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.
肌醇发挥许多细胞功能，包括渗透保护、膜功能和次级信号传递。其 Na/肌醇协同转运蛋白 SLC5A3 表达在肌肉组织中，并在肌炎中进一步积累。在这项研究中，我们专注于散发性包涵体肌炎 (IBM) 的特殊亚组，其中存在自身炎症反应和退行性变化并存。选择了一组 9 名经临床证实的 IBM 患者，使用免疫荧光法对不同组织成分进行 SLC5A3 蛋白的免疫定位，并使用 Western blot 评估表达水平。在正常肌肉组织中，SLC5A3 表达仅限于血管，肌肉纤维膜上偶尔有低水平表达。在 IBM 组织中，SLC5A3 染色明显增加，肌纤维膜不连续染色，SLC5A3 在包涵体附近和空泡边缘积聚。肌内浸润的自身攻击性免疫细胞亚群呈 SLC5A3 阳性，其中大多数是 T 细胞和 M1 谱系巨噬细胞。我们得出结论，SLC5A3 在 IBM 肌肉中过度表达，与蛋白聚集和炎症浸润有关。基于我们的结果，可以启动功能研究，探索治疗渗透剂途径干预以防止肌肉细胞中蛋白聚集的可能性。
