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Войти в исследования Rheumatology (Oxford, England) · 2025
High levels of EPSTI1 enhance IFN-β-mediated HLA-A expression and chemokine secretion in myoblasts in dermatomyositis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Li Xiaojing, Ding Ting, Xiao Yizhi, Zhou Junyu, Huang Ting, Xie Shasha, Meng Qiming, He Weijia, Zhu Hongling, Luo Hui
Аннотация
OBJECTIVES: Epithelial-Stromal Interaction 1 (EPSTI1), an IFN-related gene that has emerged as a gene of notable interest, plays a multifaceted role in cellular function and disease processes. However, the precise role of EPSTI1 in the context of DM remains elusive and requires further exploration.
METHODS: To investigate EPSTI1 expression in DM, we analysed two transcriptome datasets, peripheral blood mononuclear cells (PBMCs) and muscle tissues from our DM cohort. We further validated the findings using RT-qPCR and immunohistochemical staining within our idiopathic inflammatory myopathy (IIM) cohort. Through small interfering RNA-mediated knockdown, we delved into the function and underlying mechanisms of EPSTI1 in DM patients.
RESULTS: EPSTI1 is significantly upregulated in both PBMCs and muscle tissues of DM patients. A notable positive correlation between EPSTI1 expression and IFN-stimulating genes accompanies this upregulation. Furthermore, EPSTI1 levels were markedly elevated in IFN-β-stimulated myoblasts. Functional studies have shown that downregulation of EPSTI1 inhibits multiple immune and inflammatory pathways, including antigen processing and presentation, chemokine-mediated signalling, IFN signalling, IL-1-mediated signalling, nuclear factor (NF)-κB-inducing kinase (NIK)/NF-κB signalling. EPSTI1 was involved in the expression of HLA-A and the secretion of chemokines in myoblasts mediated by IFN-β.
CONCLUSION: EPSTI1 might play an essential role in promoting muscle inflammation in DM by regulating the expression of HLA-A and the secretion of chemokines in myoblasts. Targeting EPSTI1 may represent a novel therapeutic approach for reducing muscle inflammation and damage in dermatomyositis (DM) patients.
METHODS: To investigate EPSTI1 expression in DM, we analysed two transcriptome datasets, peripheral blood mononuclear cells (PBMCs) and muscle tissues from our DM cohort. We further validated the findings using RT-qPCR and immunohistochemical staining within our idiopathic inflammatory myopathy (IIM) cohort. Through small interfering RNA-mediated knockdown, we delved into the function and underlying mechanisms of EPSTI1 in DM patients.
RESULTS: EPSTI1 is significantly upregulated in both PBMCs and muscle tissues of DM patients. A notable positive correlation between EPSTI1 expression and IFN-stimulating genes accompanies this upregulation. Furthermore, EPSTI1 levels were markedly elevated in IFN-β-stimulated myoblasts. Functional studies have shown that downregulation of EPSTI1 inhibits multiple immune and inflammatory pathways, including antigen processing and presentation, chemokine-mediated signalling, IFN signalling, IL-1-mediated signalling, nuclear factor (NF)-κB-inducing kinase (NIK)/NF-κB signalling. EPSTI1 was involved in the expression of HLA-A and the secretion of chemokines in myoblasts mediated by IFN-β.
CONCLUSION: EPSTI1 might play an essential role in promoting muscle inflammation in DM by regulating the expression of HLA-A and the secretion of chemokines in myoblasts. Targeting EPSTI1 may represent a novel therapeutic approach for reducing muscle inflammation and damage in dermatomyositis (DM) patients.