Role of immune cell infiltration and small molecule drugs in adhesive capsulitis: Novel exploration based on bioinformatics analyses.

Role of immune cell infiltration and small molecule drugs in adhesive capsulitis: Novel exploration based on bioinformatics analyses.
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免疫细胞浸润和小分子药物在粘合胶炎中的作用:基于生物信息学分析的新型探索。

DOI:
10.3389/fimmu.2023.1075395
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发表时间:
2023
影响因子:
7.3
通讯作者:
Fu, Ming
Fu, Ming
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Hailong;Yu, Baoxi;Deng, Zengfa;Zhao, Hang;Zeng, Anyu;Li, Ruiyun;Fu, Ming

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粘连性囊炎(AC)是一种导致肩关节疼痛、僵硬和活动受限的关节炎。AC的发病机制仍存在争议。本研究旨在探讨免疫相关因素在AC发生发展中的作用。AC数据集从基因表达总括数据库(GEO)下载。根据R包“DESeq2”和Immport数据库获得差异表达的免疫相关基因(DEIRGs)。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)研究DEIRGs的功能相关性。采用MCC法和最小绝对收缩选择算子(LASSO)回归方法对HUB基因进行识别。CIBERSORTx法检测AC组和对照组肩关节囊内免疫细胞的浸润情况,Spearman等级相关分析Hub基因与免疫细胞浸润的关系。最后,通过连接性图谱数据库(Cmap)筛选出可能用于AC的小分子药物,并通过分子对接进一步验证。在AC和对照组织之间筛选出137个DEIRG和8个不同类型的显著浸润性免疫细胞(M0巨噬细胞、M1巨噬细胞、调节性T细胞、Tfh细胞、单核细胞、活化的NK细胞、记忆静止的CD4+T细胞和静止的树突状细胞)。MMP9、FOS、SOCS3和EGF是AC的潜在靶点。MMP9与记忆静息的CD4+T细胞和活化的NK细胞呈负相关,与M0巨噬细胞呈正相关。SOCS3与M1巨噬细胞呈正相关。FOS与M1巨噬细胞呈正相关。EGF与单核细胞呈正相关。此外,达克利西布(排名第一)被确定为一种潜在的小分子药物,用于AC的靶向治疗。这是对AC免疫细胞浸润分析的首次研究,这些发现可能为AC的诊断和治疗提供新的思路。
Adhesive capsulitis (AC) is a type of arthritis that causes shoulder joint pain, stiffness, and limited mobility. The pathogenesis of AC is still controversial. This study aims to explore the role of immune related factors in the occurrence and development of AC. The AC dataset was downloaded from Gene Expression Omnibus (GEO) data repository. Differentially expressed immune-related genes (DEIRGs) were obtained based on R package “DESeq2” and Immport database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to explore the functional correlation of DEIRGs. MCC method and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the hub genes. The immune cell infiltration in shoulder joint capsule between AC and control was evaluated by CIBERSORTx, and the relationship between hub genes and infiltrating immune cells was analyzed by Spearman’s rank correlation. Finally, potential small molecule drugs for AC were screened by the Connectivity Map database (CMap) and further verified by molecular docking. A total of 137 DEIRGs and eight significantly different types of infiltrating immune cells (M0 macrophages, M1 macrophages, regulatory T cells, Tfh cells, monocytes, activated NK cells, memory resting CD4+T cells and resting dendritic cells) were screened between AC and control tissues. MMP9, FOS, SOCS3, and EGF were identified as potential targets for AC. MMP9 was negatively correlated with memory resting CD4+T cells and activated NK cells, but positively correlated with M0 macrophages. SOCS3 was positively correlated with M1 macrophages. FOS was positively correlated with M1 macrophages. EGF was positively correlated with monocytes. Additionally, dactolisib (ranked first) was identified as a potential small-molecule drug for the targeted therapy of AC. This is the first study on immune cell infiltration analysis in AC, and these findings may provide a new idea for the diagnosis and treatment of AC.
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