■多发性肌炎(PM)和皮肌炎(DM)是特发性炎性肌病的两个不同亚组。胰岛素异常病,由dysferlin基因突变引起的,通常在青春期后期出现肌肉无力,退行性肌肉变化通常伴有炎症浸润,常误诊为多发性肌炎。
■为了确定与多发性肌炎相关的差异生物学途径和枢纽基因,利用生物信息学分析了解皮肌炎和脱胎症的病理机制,并为治疗的发展提供指导。
■我们分析了来自七个皮肌炎的肌内核糖核酸(RNA)测序数据,八种多发性肌炎,8名糖尿病肾病和5名对照受试者。通过使用DESeq2鉴定差异表达基因(DEGs)。进行富集分析以了解DEGs的功能和富集途径。构建了蛋白质-蛋白质相互作用(PPI)网络,并利用分子复合物检测工具(MCODE)分析明确了该基因簇,以识别hub基因。
■在DM中总共检测到1,048、179和3,807DEG,PM和异常胰岛素病,分别。富集分析显示,在DM中,上调的DEGs参与1型干扰素(IFN1)信号通路,PM中的抗原加工和肽抗原的呈递,和细胞对刺激的反应。PPI网络和MCODE簇确定了23个与DM中1型干扰素信号通路相关的基因,4个基因(PDIA3,HLA-C,B2M,和TAP1)与PM中MHC1类的形成和质量控制有关,和7个基因(HSPA9,RPTOR,MTOR,LAMTOR1,LAMTOR5,ATP6V0D1和ATP6V0B)与异常铁病患者对应激反应的细胞反应有关。
■在DM和PM中鉴定出与IFN1信号通路和主要组织相容性复合体(MHC)I类形成相关的基因的过表达,分别。在异常铁蛋白病中,检测到HSPA9和mTORC1信号通路基因的过表达。
UNASSIGNED: Polymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies.
Dysferlinopathy, caused by a dysferlin gene mutation, usually presents in late adolescence with muscle weakness, degenerative muscle changes are often accompanied by inflammatory infiltrates, often resulting in a misdiagnosis as polymyositis.
UNASSIGNED: To identify differential biological pathways and hub genes related to polymyositis, dermatomyositis and
dysferlinopathy using bioinformatics analysis for understanding the pathomechanisms and providing guidance for therapy development.
UNASSIGNED: We analyzed intramuscular ribonucleic acid (RNA) sequencing data from seven dermatomyositis, eight polymyositis, eight dysferlinopathy and five control subjects. Differentially expressed genes (DEGs) were identified by using DESeq2. Enrichment analyses were performed to understand the functions and enriched pathways of DEGs. A protein-protein interaction (PPI) network was constructed, and clarified the gene cluster using the molecular complex detection tool (MCODE) analysis to identify hub genes.
UNASSIGNED: A total of 1,048, 179 and 3,807 DEGs were detected in DM, PM and
dysferlinopathy, respectively. Enrichment analyses revealed that upregulated DEGs were involved in type 1 interferon (IFN1) signaling pathway in DM, antigen processing and presentation of peptide antigen in PM, and cellular response to stimuli in
dysferlinopathy. The PPI network and MCODE cluster identified 23 genes related to type 1 interferon signaling pathway in DM, 4 genes (PDIA3, HLA-C, B2M, and TAP1) related to MHC class 1 formation and quality control in PM, and 7 genes (HSPA9, RPTOR, MTOR, LAMTOR1, LAMTOR5, ATP6V0D1, and ATP6V0B) related to cellular response to stress in dysferliniopathy.
UNASSIGNED: Overexpression of genes related to the IFN1 signaling pathway and major histocompatibility complex (MHC) class I formation was identified in DM and PM, respectively. In
dysferlinopathy, overexpression of HSPA9 and the mTORC1 signaling pathway genes was detected.