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
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DOI：
10.3390/biom10040521
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发表时间：
2020-04-01
期刊：
影响因子：
5.5
通讯作者：
De Bleecker, Jan L.
中科院分区：
文献类型：
--
作者：
De Paepe, Boel;Merckx, Caroline;De Bleecker, Jan L.
肌醇发挥许多细胞功能，包括渗透保护、膜功能和次级信息传递。其Na+/肌醇协同转运蛋白SLC5A3在肌肉组织中表达，并在肌炎中进一步积累。在这项研究中，我们重点关注散发性包涵体肌炎（IBM）这一特殊亚组，其中自身炎症反应和退行性变化同时存在。选择了由临床证实的 IBM 的 9 名患者组成的队列，其中使用免疫荧光将 SLC5A3 蛋白免疫定位到不同的组织成分，并使用蛋白质印迹评估表达水平。在正常肌肉组织中，SLC5A3 表达仅限于血管，偶尔在肌纤维膜上表达较低水平。在IBM组织中，SLC5A3染色显着增加，肌纤维膜染色不连续，并且SLC5A3在包涵体附近和液泡边缘积累。肌肉浸润的自身攻击性免疫细胞的一个子集呈 SLC5A3 阳性，其中大多数是 T 细胞和 M1 谱系巨噬细胞。我们得出的结论是，SLC5A3 在 IBM 肌肉中过度表达，与蛋白质聚集和炎症浸润相关。根据我们的结果，可以启动功能研究来探索治疗性渗透剂途径干预以防止肌肉细胞中蛋白质聚集的可能性。
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.