Global analysis of protein expression in muscle tissues of dermatomyositis/polymyosisits patients demonstrated an association between dysferlin and human leucocyte antigen A
Global analysis of protein expression in muscle tissues of dermatomyositis/polymyosisits patients demonstrated an association between dysferlin and human leucocyte antigen A
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对皮肌炎/多发性肌病患者肌肉组织中蛋白质表达的整体分析表明，dysferlin 与人类白细胞抗原 A 之间存在关联
DOI：
10.1093/rheumatology/kez085
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发表时间：
2019
期刊：
影响因子：
5.5
通讯作者：
Zuo Xiaoxia
中科院分区：
文献类型：
--
作者：
Xiao Yizhi;Zhu Honglin;Li Liya;Gao Siming;Liu Di;Dai Bingying;Li Qiuxiang;Duan Huiqian;Yang Huan;Li Quanzhen;Zhang Huali;Luo Hui;Zuo Xiaoxia
目的：DM和PM以肌纤维损伤和炎性细胞浸润为特征，主要表现为MHC I类分子HLA-A和单核细胞趋化蛋白-1（MCP-1）的高表达。Dysferlin（DYSF）是一种跨膜糖蛋白，锚定在肌纤维的肌膜中。DYSF突变与遗传性肌病密切相关。本研究旨在确定DYSF在DM/PM的发展中的作用。MethodsMS在DM/PM患者和对照组的肌肉组织中进行。采用免疫印迹法、免疫荧光法、流式细胞术和酶联免疫吸附法检测肌肉组织、外周血细胞和血清中DYSF的含量。结果质谱分析和生物信息学分析结果表明，DM/PM患者中表达异常的蛋白质参与了DM/PM患者常见的生物学过程和途径，如前体代谢产物和能量的产生。DM/PM患者肌肉组织和血清中DYSF表达上调。DYSF主要表达于肌纤维，与HLA-A和MCP-1共定位。在患者血清和IFN-β刺激下，心肌细胞和内皮细胞DYSF和HLA-A的表达增加。然而，没有直接的相互作用，发现DYSF和HLA-A之间的免疫共沉淀。ConclusionOur研究揭示了在DM/PM患者样本中参与共同和特定的生物过程的失调蛋白。在DM/PM的发展过程中，DYSF被上调并与HLA-A和MCP-1一起在炎性细胞浸润和肌肉损伤中显示出沿着的潜在作用。
ObjectivesDM and PM are characterized by myofibre damage with inflammatory cell infiltration due to the strong expressions of MHC class I HLA-A and monocyte chemoattractant protein-1 (MCP-1). Dysferlin (DYSF) is a transmembrane glycoprotein that anchors in the sarcolemma of myofibres. DYSF mutation is closely associated with inherited myopathies. This study aimed to determine the role of DYSF in the development of DM/PM.MethodsMass spectrometry was performed in muscle tissues from DM/PM patients and controls. The DYSF levels in muscle tissue, peripheral blood cells and serum were detected by Western blotting, IF, flow cytometry or ELISA. Double IF and co-immunoprecipitation were used to investigate the relationship between DYSF and HLA-A.ResultsMass spectrometry and bioinformatics analysis findings suggested the dysregulated proteins in DM/PM patients participated in common biological processes and pathways, such as the generation of precursor metabolites and energy. DYSF was upregulated in the muscle tissue and serum of DM/PM patients. DYSF was mainly expressed in myofibres and co-localized with HLA-A and MCP-1. DYSF and HLA-A expressions were elevated in myocytes and endothelial cells after being stimulated by patient serum and IFN-β. However, no direct interactions were found between DYSF and HLA-A by co-immunoprecipitation.ConclusionOur study revealed the dysregulated proteins involved in common and specific biological processes in DM/PM patient samples. DYSF is upregulated and exhibits a potential role along with that of HLA-A and MCP-1 in inflammatory cell infiltration and muscle damage during the development of DM/PM.