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首页> 外文期刊>Cellular Signalling >Upregulation of p16 ~(INK4A)promotes cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients
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Upregulation of p16 ~(INK4A)promotes cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients

机译:p16〜(INK4A)的上调促进系统性红斑狼疮患者骨髓间充质干细胞的细胞衰老

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摘要

Previous studies have indicated that bone marrow-derived mesenchymal stem cells(MSCs)from patients with systemic lupus erythematosus(SLE)exhibited impaired proliferation, differentiation, and immune modulation capacities. Thus, MSCs may be associated with the pathogenesis of SLE. The aim of this study was to determine whether MSCs from SLE patients were senescent and to determine the mechanism underlying this phenomenon. MSCs from both untreated and treated SLE patients showed characteristics of senescence. The expression of p16 ~(INK4A)was significantly increased, whereas levels of CDK4, CDK6 and p-Rb expression were decreased in the MSCs from both untreated and treated SLE patients. Knockdown of p16 ~(INK4A)expression reversed the senescent features of MSCs and upregulated TGF-β expression. In vitro, when purified CD4+ T cells were incubated with p16 ~(INK4A)-silenced SLE MSCs, the percentage of regulatory T cells was significantly increased. Further, we have found that p16 ~(INK4A)promotes MSC senescence via the suppression of the extracellular signal regulated kinase(ERK)pathway. p16 ~(INK4A)knockdown up-regulated ERK1/2 activation. Our results demonstrated that MSCs from SLE patients were senescent and that p16 ~(INK4A)plays an essential role in the process by inhibiting ERK1/2 activation.
机译:先前的研究表明,系统性红斑狼疮(SLE)患者的骨髓间充质干细胞(MSC)表现出受损的增殖,分化和免疫调节能力。因此,MSC可能与SLE的发病机制有关。这项研究的目的是确定SLE患者的MSC是否衰老,并确定这种现象的潜在机制。未治疗和治疗过的SLE患者的MSC均显示衰老特征。未治疗和已治疗的SLE患者的MSC中,p16〜(INK4A)的表达显着增加,而CDK4,CDK6和p-Rb的表达降低。抑制p16〜(INK4A)表达可逆转MSC的衰老特征并上调TGF-β表达。在体外,当将纯化的CD4 + T细胞与沉默了p16〜(INK4A)的SLE MSC孵育时,调节性T细胞的百分比显着增加。此外,我们发现p16〜(INK4A)通过抑制细胞外信号调节激酶(ERK)途径促进MSC衰老。 p16〜(INK4A)敲低ERK1 / 2激活。我们的结果表明,SLE患者的MSCs处于衰老状态,p16〜(INK4A)通过抑制ERK1 / 2激活在该过程中起重要作用。

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