Repeated stimulation by LPS promotes the senescence of DPSCs via TLR4/MyD88-NF-κB-p53/p21 signaling
Repeated stimulation by LPS promotes the senescence of DPSCs via TLR4/MyD88-NF-κB-p53/p21 signaling
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DOI：
10.1007/s10616-017-0180-6
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发表时间：
2018-06-01
期刊：
影响因子：
2.2
通讯作者：
Feng, Xingmei
中科院分区：
文献类型：
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作者：
Feng, Guijuan;Zheng, Ke;Feng, Xingmei
牙髓干细胞（DPSCs）是间充质干细胞的一种，被认为是再生医学和组织工程的工具细胞。我们前期研究发现脂多糖（LPS）刺激可引起DPSCs的衰老，且其衰老与LPS浓度呈正相关。采用β -半乳糖苷酶（sa - β -gal）染色评价DPSCs的衰老程度，免疫荧光显示DPSCs的形态。我们的研究结果表明，在LPS的反复刺激下，sa - β -gal的活性增加，DPSCs的形态也随着LPS的刺激发生了变化。我们还发现LPS与toll样受体4 (TLR4)/髓样分化因子（MyD） 88信号通路结合。LPS刺激后，DPSCs中TLR4、MyD88蛋白及mRNA表达增强，导致核因子κ B （nf - κ B）信号通路激活，细胞核中p65表达增强，I κ B- α表达降低。同时，nf - κ B信号下游蛋白p53和p21的表达增加。综上所述，在炎症微环境中反复刺激后，DPSCs容易发生衰老。最终，这些发现可能会为口腔疾病和其他再生药物的细胞治疗带来新的方向。
Dental pulp stem cells (DPSCs), one type of mesenchymal stem cells, are considered to be a type of tool cells for regenerative medicine and tissue engineering. Our previous studies found that the stimulation with lipopolysaccharide (LPS) might introduce senescence of DPSCs, and this senescence would have a positive correlation with the concentration of LPS. The beta-galactosidase (SA-beta-gal) staining was used to evaluate the senescence of DPSCs and immunofluorescence to show the morphology of DPSCs. Our findings suggested that the activity of SA-beta-gal has increased after repeated stimulation with LPS and the morphology of DPSCs has changed with the stimulation with LPS. We also found that LPS bound to the Toll-like receptor 4 (TLR4)/myeloid differentiation factor (MyD) 88 signaling pathway. Protein and mRNA expression of TLR4, MyD88 were enhanced in DPSCs with LPS stimulation, resulting in the activation of nuclear factor-kappa B (NF-kappa B) signaling, which exhibited the expression of p65 improved in the nucleus while the decreasing of I kappa B-alpha. Simultaneously, the expression of p53 and p21, the downstream proteins of the NF-kappa B signaling, has increased. In summary, DPSCs tend to undergo senescence after repeated stimulation in an inflammatory microenvironment. Ultimately, these findings may lead to a new direction for cell-based therapy in oral diseases and other regenerative medicines.