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Nuclear Nox4 interaction with prelamin A is associated with nuclear redox control of stem cell aging

机译:核Nox4与prelamin A的相互作用与干细胞衰老的核氧化还原控制有关

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摘要

Mesenchymal stem cells have emerged as an important tool that can be used for tissue regeneration thanks to their easy preparation, differentiation potential and immunomodulatory activity. However, an extensive culture of stem cells in vitro prior to clinical use can lead to oxidative stress that can modulate different stem cells properties, such as self-renewal, proliferation, differentiation and senescence. The aim of this study was to investigate the aging process occurring during in vitro expansion of stem cells, obtained from amniotic fluids (AFSC) at similar gestational age.The analysis of 21 AFSC samples allowed to classify them in groups with different levels of stemness properties. In summary, the expression of pluripotency genes and the proliferation rate were inversely correlated with the content of reactive oxygen species (ROS), DNA damage signs and the onset premature aging markers, including accumulation of prelamin A, the lamin A immature form. Interestingly, a specific source of ROS, the NADPH oxidase isoform 4 (Nox4), can localize into PML nuclear bodies (PML-NB), where it associates to prelamin A. Besides, Nox4 post translational modification, involved in PML-NB localization, is linked to its degradation pathway, as it is also for prelamin A, thus possibly modulating the premature aging phenotype occurrence.
机译:间充质干细胞由于其易于制备,分化潜能和免疫调节活性,已成为可用于组织再生的重要工具。但是,在临床使用之前在体外广泛培养干细胞会导致氧化应激,这种氧化应激可调节不同的干细胞特性,例如自我更新,增殖,分化和衰老。这项研究的目的是研究从类似胎龄的羊水(AFSC)获得的干细胞在体外扩增过程中发生的衰老过程。对21个AFSC样品的分析可以将它们分为具有不同干性水平的组。总之,多能性基因的表达和增殖速率与活性氧(ROS)的含量,DNA损伤征象和发病的早衰标志物(包括prelamin A的积累,lamin A的未成熟形式)成反比。有趣的是,特定的ROS来源NADPH氧化酶同工型4(Nox4)可以定位在PML核小体(PML-NB)中,并与prelamin A结合。此外,翻译后修饰的Nox4参与了PML-NB的定位,如同其对prelamin A的作用一样,它与它的降解途径有关,因此可能调节过早衰老的表型的发生。

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