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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Dampened ERK signaling in hematopoietic progenitor cells in rheumatoid arthritis
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Dampened ERK signaling in hematopoietic progenitor cells in rheumatoid arthritis

机译：类风湿关节炎造血祖细胞中ERK信号减弱

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In rheumatoid arthritis (RA), hematopoietic progenitor cells (HPC) have age-inappropriate telomeric shortening suggesting premature senescence and possible restriction of proliferative capacity. In response to hematopoietic growth factors RA-derived CD34 + HPC expanded significantly less than age-matched controls. Cell surface receptors for stem cell factor (SCF), Flt 3-Ligand, IL-3 and IL-6 were intact in RA HPC but the cells had lower transcript levels of cell cycle genes, compatible with insufficient signal strength in the ERK pathway. Cytokine-induced phosphorylation of ERK1/2 was diminished in RA HPC whereas phosphorylated STAT3 and STAT5 molecules accumulated to a similar extent as in controls. Confocal microscopy demonstrated that the membrane-proximal colocalization of K-Ras and B-Raf was less efficient in RA-derived CD34 + cells. Thus, hyporesponsiveness of RA HPC to growth factors results from dampening of the ERK signaling pathways; with a defect localized in the very early steps of the ERK signaling cascade.
机译：在类风湿关节炎（RA）中，造血祖细胞（HPC）具有年龄不适当的端粒缩短，提示过早衰老并可能限制了增殖能力。响应造血生长因子，RA衍生的CD34 + HPC的扩增明显少于年龄匹配的对照。 RA HPC中干细胞因子（SCF），Flt 3-配体，IL-3和IL-6的细胞表面受体完好无损，但细胞的细胞周期基因转录水平较低，与ERK途径的信号强度不足兼容。 RA HPC中细胞因子诱导的ERK1 / 2磷酸化减少，而磷酸化的STAT3和STAT5分子积累的程度与对照组相似。共聚焦显微镜表明，在RA衍生的CD34 +细胞中，K-Ras和B-Raf的膜近共定位效率较低。因此，RA HPC对生长因子的低反应性是由于ERK信号通路的减弱引起的。缺陷位于ERK信号级联的早期阶段。

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