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PMEPA1-Mediated Treg Cell Impairment Promotes Endometrial Stromal Invasion via Excessive PI3K/AKT Signaling in Endometriosis 认领 引用
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作者 Ya-qin Peng Lu Wang +4 位作者 Ai-li Tan Shu-jun Wang Wen Zou Xing Li Jing Yang 《Current Medical Science》 SCIE CAS CSCD 2025年第5期1231-1243,共13页
Objective Although immune dysregulation is implicated in the pathogenesis of endometriosis(EMs),the specific role of prostate transmembrane protein androgen induced 1(PMEPA1)in modulating the function of regulatory T ... Objective Although immune dysregulation is implicated in the pathogenesis of endometriosis(EMs),the specific role of prostate transmembrane protein androgen induced 1(PMEPA1)in modulating the function of regulatory T cells(Tregs)remains inadequately understood.This study aimed to elucidate the regulatory mechanisms by which PMEPA1 influences the activity of Tregs,thereby facilitating the invasion of endometrial stromal cells(ESCs).Methods Single-cell RNA sequencing(scRNA-seq)was performed on matched ectopic ovarian lesions and eutopic endometria from 3 patients.Clinical specimens from patients with EMs and control subjects were examined for PMEPA1 expression.Primary human Tregs isolated from peripheral blood mononuclear cells were subjected to PMEPA1 overexpression(via plasmid)or knockdown(via siRNA).Modulation of the PI3K pathway was conducted via the activator 740Y-P or the inhibitor LY294002.The secretion of IL-10 and TGF-βby Tregs was quantified using an enzyme-linked immunosorbent assay.Ectopic ESCs cocultured with modified Tregs were assessed for their proliferation,migration,and invasion capabilities.Results scRNA-seq data revealed significant upregulation of PMEPA1 in Tregs from ectopic ovarian lesions compared with paired eutopic endometria.PMEPA1 expression was increased in the ectopic lesions and peritoneal fluid mononuclear cells of patients with EMs.Tregs overexpressing PMEPA1 demonstrated reduced secretion of IL-10 and TGF-βbut exhibited hyperactivation of the PI3K/AKT signaling pathway.Treatment with LY294002 ameliorated the impairment in cytokine secretion.Coculture experiments with Tregs expressing high levels of PMEPA1 resulted in increased invasion,migration,and proliferation of ESCs.Conclusion PMEPA1 impairs Treg-mediated immunosuppression by hyperactivating the PI3K/AKT pathway,thereby facilitating the invasiveness of ESCs in EMs. 展开更多
关键词 Prostate transmembrane protein androgen induced 1 Regulatory T cells PI3K/AKT signaling Endometriosis Stromal cells
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