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肌动蛋白生长分化因子15(GDF-15)是一种潜在的肌炎生物标志物,与散发性包涵体肌炎的蛋白质聚集体相关。

The myokine GDF-15 is a potential biomarker for myositis and associates with the protein aggregates of sporadic inclusion body myositis.

作者信息

De Paepe Boel, Verhamme Fien, De Bleecker Jan L

机构信息

Department of Neurology and Neuromuscular Reference Centre, Ghent University Hospital, Ghent, Belgium.

Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.

出版信息

Cytokine. 2020 Mar;127:154966. doi: 10.1016/j.cyto.2019.154966. Epub 2020 Jan 2.

Abstract

BACKGROUND

The cytokine growth differentiation factor-15 (GDF-15) has been associated with inflammatory and mitochondrial disease, warranting exploration of its expression in myositis patients.

METHODS

GDF-15 protein levels are evaluated in 35 idiopathic inflammatory myopathy (IIM) serum samples using enzyme-linked immunosorbent assays, comparing with levels in samples from healthy individuals and from patients with genetically confirmed hereditary muscular dystrophies and mitochondrial disorders. Muscle tissue expression of GDF-15 protein is evaluated using immunofluorescent staining and Western blotting.

RESULTS

GDF-15 protein levels are significantly higher in IIM sera (625 ± 358 pg/ml) than in that of healthy controls (326 ± 204 pg/ml, p = 0.01). Western blotting confirms increased GDF-15 protein levels in IIM muscle. In skeletal muscle tissue of IIM patients, GDF-15 localizes mostly to small regenerating or denervated muscle fibres. In patients diagnosed with sporadic inclusion body myositis, GDF-15 co-localizes with the characteristic protein aggregates within affected muscle fibres.

CONCLUSIONS

We describe for the first time that GDF-15 is a myokine upregulated in myositis and present the cytokine as a potential diagnostic serum biomarker.

摘要

背景

细胞因子生长分化因子15(GDF-15)与炎症和线粒体疾病有关,因此有必要探索其在肌炎患者中的表达情况。

方法

采用酶联免疫吸附测定法评估35例特发性炎性肌病(IIM)血清样本中的GDF-15蛋白水平,并与健康个体、基因确诊的遗传性肌营养不良症和线粒体疾病患者样本中的水平进行比较。使用免疫荧光染色和蛋白质印迹法评估肌肉组织中GDF-15蛋白的表达。

结果

IIM血清中的GDF-15蛋白水平(625±358 pg/ml)显著高于健康对照组(326±204 pg/ml,p = 0.01)。蛋白质印迹法证实IIM肌肉中GDF-15蛋白水平升高。在IIM患者的骨骼肌组织中,GDF-15主要定位于小的再生或失神经支配的肌纤维。在诊断为散发性包涵体肌炎的患者中,GDF-15与受影响肌纤维内的特征性蛋白聚集体共定位。

结论

我们首次描述了GDF-15是一种在肌炎中上调的肌动蛋白,并将该细胞因子作为一种潜在的诊断血清生物标志物。

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