原发性斯约格伦综合征中热蛋白沉积相关枢纽基因和免疫微环境的研究。

IF 3.4 4区 医学 Q2 RHEUMATOLOGY
Weilu Chen, Wanling Chen, Ning Xia, Ruyu Yan
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引用次数: 0

摘要

研究目的原发性斯约格伦综合征(pSS)是一种炎症性系统性自身免疫疾病,而嗜热症在pSS中的作用和机制在很大程度上仍未确定:方法:从分子特征数据库(Molecular Signatures Database)和 NCBI GEO 数据库中获取热蛋白沉积相关基因和基因表达数据。用R软件识别差异表达基因(DEGs)和与pyroptosis相关的枢纽基因。使用 "ClusterProfiler "R软件包和WebGestalt7进行功能富集分析。CIBERSORTx 用于计算免疫细胞与化脓过程之间的相关性。随后,对非 pSS 和 pSS 患者的唾液腺样本进行了组织学染色,以确定热蛋白沉着相关基因的表达。免疫荧光双重染色验证了免疫细胞与化脓过程的相关性:结果:8 个 pSS 样本和 10 个健康志愿者样本共鉴定出 1494 个 DEGs。结果:8 个 pSS 样本和 10 个健康志愿者样本共鉴定出 1494 个 DEGs,其中 5 个与化脓相关的枢纽基因(AIM2、CASP1、CASP3、IL6、TNF)被确认。DEGs大多富集在免疫相关的术语中,有几个免疫细胞与pSS中的枢纽基因相关。其中,δγ T 细胞与 CASP3 呈显著正相关。最后,通过免疫组化染色法验证了与健康志愿者相比,pSS 患者唇小唾液腺活检组织中这些中心基因的蛋白水平升高。免疫荧光双重染色进一步表明,IL-6、AIM2、CASP1和CASP3与δγT细胞有关,而TNF与树突状细胞有关:结论:本研究揭示了pSS患者体内的脓毒症与免疫微环境之间的重要相互作用。结论:本研究发现了 pSS 患者体内热蛋白沉积与免疫微环境之间的重要相互作用,并发现了五个可能在 pSS 发病机制中发挥作用的热蛋白沉积相关枢纽基因。这些发现可为开发治疗 pSS 的新策略提供有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Investigation of pyroptosis-related hub genes and the immune microenvironment in primary Sjögren's syndrome.

Objectives: Primary Sjögren's syndrome (pSS) is an inflammatory systemic autoimmune disease, while the role and mechanisms of pyroptosis in pSS remain largely undefined.

Methods: Pyroptosis-related genes and gene expression data were obtained from the Molecular Signatures Database and NCBI GEO databases. Differentially expressed genes (DEGs) and pyroptosis-related hub genes were identified by R software. Functional enrichment analyses were conducted using the "ClusterProfiler" R package and WebGestalt7. CIBERSORTx was used to calculate the correlations between immune cells and pyroptosis. Subsequently, histological staining was performed on salivary gland samples from non-pSS and pSS patients to identify the expression of pyroptosis-related genes. Immunofluorescence double staining was conducted to validate the correlation between immune cells and pyroptosis.

Results: A total of 1494 DEGs were identified between eight pSS samples and 10 healthy volunteer samples. Five pyroptosis-related hub genes (AIM2, CASP1, CASP3, IL6, TNF) were recognised. DEGs were mostly enriched in immunity-related terms and several immune cells were associated with the hub genes in pSS. Among them, delta gamma T cell was significantly positively correlated with CASP3. Finally, the protein levels of these hub genes were validated to be elevated in the labial minor salivary gland biopsies of pSS patients compared to those of healthy volunteers using immunohistochemical staining. Immunofluorescence double staining further showed that IL-6, AIM2, CASP1and CASP3 were related to delta gamma T cells, and TNF was related to dendritic cells.

Conclusions: This study uncovered a significant interaction between pyroptosis and the immune microenvironment in pSS patients. Besides, we identified five pyroptosis-related hub genes that might play a role in the pathogenesis of pSS. These findings could offer valuable insights for the development of novel treatment strategies for pSS.

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来源期刊
CiteScore
6.10
自引率
18.90%
发文量
377
审稿时长
3-6 weeks
期刊介绍: Clinical and Experimental Rheumatology is a bi-monthly international peer-reviewed journal which has been covering all clinical, experimental and translational aspects of musculoskeletal, arthritic and connective tissue diseases since 1983.
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