Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis.
Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis.
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DOI：
10.1186/s13075-017-1303-3
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发表时间：
2017-05-31
影响因子：
4.9
通讯作者：
Guma M
中科院分区：
文献类型：
--
作者：
Bustamante MF;Garcia-Carbonell R;Whisenant KD;Guma M
越来越多的研究表明，细胞内代谢途径的变化如何改变肿瘤和免疫细胞的功能。然而，关于其他细胞类型（包括滑膜成纤维细胞）代谢变化的信息很少。在类风湿性关节炎（RA）中，成纤维细胞样滑膜细胞（FLS）是pannus -软骨连接处最常见的细胞类型，通过产生细胞因子、趋化因子和基质降解分子以及迁移和侵入关节软骨来破坏关节。在这篇综述中，我们发现这些细胞与健康的滑膜成纤维细胞不同，不仅在它们的标记物表达、原癌基因表达或它们的表观遗传变化上，而且在它们的细胞内代谢上。这些代谢变化必须发生在炎症组织的应激微环境中，其中葡萄糖、谷氨酰胺和氧气等关键营养物质的浓度在空间和时间上都是不均匀的。此外，这些代谢变化将增加成纤维细胞和其他滑膜细胞之间的代谢物交换，这可能被潜在地激活。葡萄糖和磷脂代谢以及生物活性脂质，包括鞘氨醇-1-磷酸和溶血磷脂酸等，都参与了FLS的激活。这些代谢变化可能导致FLS参与免疫反应启动或异常免疫反应的各个方面，并强烈促进关节破坏。
An increasing number of studies show how changes in intracellular metabolic pathways alter tumor and immune cell function. However, little information about metabolic changes in other cell types, including synovial fibroblasts, is available. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are the most common cell type at the pannus–cartilage junction and contribute to joint destruction through their production of cytokines, chemokines, and matrix-degrading molecules and by migrating and invading joint cartilage. In this review, we show that these cells differ from healthy synovial fibroblasts, not only in their marker expression, proto-oncogene expression, or their epigenetic changes, but also in their intracellular metabolism. These metabolic changes must occur due to the stressful microenvironment of inflamed tissues, where concentrations of crucial nutrients such as glucose, glutamine, and oxygen are spatially and temporally heterogeneous. In addition, these metabolic changes will increase metabolite exchange between fibroblast and other synovial cells, which can potentially be activated. Glucose and phospholipid metabolism as well as bioactive lipids, including sphingosine-1-phosphate and lysophosphatidic acid, among others, are involved in FLS activation. These metabolic changes likely contribute to FLS involvement in aspects of immune response initiation or abnormal immune responses and strongly contribute to joint destruction.