PDF(Pubmed)
Abstract：
Psoriasis is an inflammatory disease mediated by helper T (Th)17 and Th1 cells. MicroRNA-125a (miR-125a) is reduced in the lesional skin of psoriatic patients. However, the mechanism by which miR-125a participates in psoriasis remains unclear.
The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4+ T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo.
miR-125a-5p was downregulated in peripheral blood CD4+ T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4+ T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells.
miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ.
The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4+ T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo.
miR-125a-5p was downregulated in peripheral blood CD4+ T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4+ T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells.
miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ.
摘要：
背景：银屑病是一种由辅助性T（Th）17和Th1细胞介导的炎性疾病。微RNA-125a(miR-125a)在银屑病患者的皮损中减少。然而,miR-125a参与银屑病的机制尚不清楚.
方法：miR-125a-5p及其下游靶标（ETS-1，IFN-γ，通过定量实时PCR（qRT-PCR）检测健康对照组和银屑病患者的CD4T细胞和STAT3）。体外，转染miR-125a-5p模拟物用于通过流式细胞术分析miR-125a-5p对Th17细胞分化的影响。咪喹莫特（IMQ）诱导的小鼠模型用于评估通过体内皮内注射agomir-125a-5p上调miR-125a-5p的作用。
结果：miR-125a-5p在银屑病患者外周血CD4+T细胞中下调，与调节性T细胞（Tregs）的比例呈正相关，与银屑病面积和严重程度指数（PASI）评分呈负相关。此外，miR-125a-5p模拟物促进Tregs的分化并下调ETS-1，IFN-γ的信使RNA（mRNA）水平，和STAT3在小鼠CD4+T细胞中。此外，agomir-125a-5p通过下调Th17细胞的比例减轻了IMQ诱导的小鼠模型中的牛皮癣样炎症。
结论：miR-125a-5p可能通过靶向STAT3恢复Tregs对Th17细胞的抑制功能，通过靶向ETS-1和IFN-γ间接恢复Tregs对Th1细胞的抑制功能，从而在银屑病中具有治疗潜力。
方法：miR-125a-5p及其下游靶标（ETS-1，IFN-γ，通过定量实时PCR（qRT-PCR）检测健康对照组和银屑病患者的CD4T细胞和STAT3）。体外，转染miR-125a-5p模拟物用于通过流式细胞术分析miR-125a-5p对Th17细胞分化的影响。咪喹莫特（IMQ）诱导的小鼠模型用于评估通过体内皮内注射agomir-125a-5p上调miR-125a-5p的作用。
结果：miR-125a-5p在银屑病患者外周血CD4+T细胞中下调，与调节性T细胞（Tregs）的比例呈正相关，与银屑病面积和严重程度指数（PASI）评分呈负相关。此外，miR-125a-5p模拟物促进Tregs的分化并下调ETS-1，IFN-γ的信使RNA（mRNA）水平，和STAT3在小鼠CD4+T细胞中。此外，agomir-125a-5p通过下调Th17细胞的比例减轻了IMQ诱导的小鼠模型中的牛皮癣样炎症。
结论：miR-125a-5p可能通过靶向STAT3恢复Tregs对Th17细胞的抑制功能，通过靶向ETS-1和IFN-γ间接恢复Tregs对Th1细胞的抑制功能，从而在银屑病中具有治疗潜力。
