Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in demyelinating pathologies including multiple sclerosis (MS). In our recent study, oligodendrocyte‐specific deletion of FGFR1 resulted in a milder disease course, less inflammation, reduced myelin and axon damage in EAE. The objective of this study was to elucidate the role of oligodendroglial FGFR2 in MOG_35‐55‐induced EAE. Oligodendrocyte‐specific knockout of FGFR2 (Fgfr2^ind−/−) was achieved by application of tamoxifen; EAE was induced using the MOG_35‐55 peptide. EAE symptoms were monitored over 62 days. Spinal cord tissue was analysed by histology, immunohistochemistry and western blot. Fgfr2^ind−/− mice revealed a milder disease course, less myelin damage and enhanced axonal density. The number of oligodendrocytes was not affected in demyelinated areas. However, protein expression of FGFR2, FGF2 and FGF9 was downregulated in Fgfr2^ind−/− mice. FGF/FGFR dependent signalling proteins were differentially regulated; pAkt was upregulated and pERK was downregulated in Fgfr2^ind−/− mice. The number of CD3(+) T cells, Mac3(+) cells and B220(+) B cells was less in demyelinated lesions of Fgfr2^ind−/− mice. Furthermore, expression of IL‐1β, TNF‐α and CD200 was less in Fgfr2^ind−/− mice than controls. Fgfr2^ind−/− mice showed an upregulation of PLP and downregulation of the remyelination inhibitors SEMA3A and TGF‐β expression. These data suggest that cell‐specific deletion of FGFR2 in oligodendrocytes has anti‐inflammatory and neuroprotective effects accompanied by changes in FGF/FGFR dependent signalling, inflammatory cytokines and expression of remyelination inhibitors. Thus, FGFRs in oligodendrocytes may represent potential targets for the treatment of inflammatory and demyelinating diseases including MS.

中文翻译：

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FGFR2的少突胶质细胞特异性缺失通过ERK和Akt信号传导改善MOG35-55诱导的EAE

成纤维细胞生长因子 (FGF) 及其受体 (FGFR) 参与脱髓鞘病理，包括多发性硬化 (MS)。在我们最近的研究中，少突胶质细胞特异性FGFR1缺失导致 EAE 中较轻的病程、较少的炎症、减少的髓鞘和轴突损伤。本研究的目的是阐明少突胶质细胞FGFR2在 MOG _35-55诱导的 EAE 中的作用。FGFR2 ( Fgfr2 ^{ind -/-} ) 的少突胶质细胞特异性敲除是通过应用他莫昔芬实现的；使用 MOG _35-55肽诱导 EAE 。在 62 天内监测 EAE 症状。通过组织学、免疫组织化学和蛋白质印迹分析脊髓组织。Fgfr2^{ind -/-}小鼠表现出较轻的病程、较少的髓鞘损伤和增强的轴突密度。脱髓鞘区域的少突胶质细胞数量不受影响。然而，FGFR2、FGF2 和 FGF9 的蛋白质表达在Fgfr2 ^{ind -/-}小鼠中下调。FGF/FGFR 依赖性信号蛋白受到差异调节；在Fgfr2 ^{ind -/-}小鼠中，pAkt 被上调而 pERK 被下调。在Fgfr2 ^{ind -/-} 小鼠的脱髓鞘病变中，CD3(+) T 细胞、Mac3(+) 细胞和 B220(+) B 细胞的数量较少。此外，IL-1β、TNF-α 和 CD200 在Fgfr2 ^{ind -/-} 小鼠中的表达低于对照。Fgfr2 ^{ind -/-} 小鼠表现出 PLP 的上调和髓鞘再生抑制剂 SEMA3A 和 TGF-β 表达的下调。这些数据表明少突胶质细胞中FGFR2的细胞特异性缺失具有抗炎和神经保护作用，伴随着 FGF/FGFR 依赖性信号、炎症细胞因子和髓鞘再生抑制剂表达的变化。因此，少突胶质细胞中的 FGFR 可能代表治疗炎症和脱髓鞘疾病（包括 MS）的潜在靶点。