Center for developmental biology and reprogramming - CEDEBIOR, Department of Biomedical Sciences, University of Sassari Viale San Pietro 43/B, 07100 Sassari, Italy.
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.
Sci Rep. 2016 Jun 24;6:28682. doi: 10.1038/srep28682.
Hyaluronic acid (HA) plays a fundamental role in cell polarity and hydrodynamic processes, affording significant modulation of proliferation, migration, morphogenesis and senescence, with deep implication in the ability of stem cells to execute their differentiating plans. The Radio Electric Asymmetric Conveyer (REAC) technology is aimed to optimize the ions fluxes at the molecular level in order to optimize the molecular mechanisms driving cellular asymmetry and polarization. Here, we show that treatment with 4-methylumbelliferone (4-MU), a potent repressor of type 2 HA synthase and endogenous HA synthesis, dramatically antagonized the ability of REAC to recover the gene and protein expression of Bmi1, Oct4, Sox2, and Nanog in ADhMSCs that had been made senescent by prolonged culture up to the 30(th) passage. In senescent ADhMSCs, 4-MU also counteracted the REAC ability to rescue the gene expression of TERT, and the associated resumption of telomerase activity. Hence, the anti-senescence action of REAC is largely dependent upon the availability of endogenous HA synthesis. Endogenous HA and HA-binding proteins with REAC technology create an interesting network that acts on the modulation of cell polarity and intracellular environment. This suggests that REAC technology is effective on an intracellular niche level of stem cell regulation.
透明质酸（HA）在细胞极性和流体动力学过程中发挥着基本作用，对增殖、迁移、形态发生和衰老具有显著的调节作用，对干细胞执行分化计划的能力有深远的影响。无线电电不对称输送（REAC）技术旨在优化分子水平的离子通量，以优化驱动细胞不对称和极化的分子机制。在这里，我们表明，用 4-甲基伞形酮（4-MU）处理，一种有效的 2 型 HA 合酶和内源性 HA 合成的抑制剂，可显著拮抗 REAC 恢复延长培养至第 30 代后衰老的 ADhMSCs 中 Bmi1、Oct4、Sox2 和 Nanog 基因和蛋白表达的能力。在衰老的 ADhMSCs 中，4-MU 也拮抗了 REAC 恢复端粒酶相关基因 TERT 表达和相关端粒酶活性的能力。因此，REAC 的抗衰老作用在很大程度上取决于内源性 HA 合成的可用性。内源性 HA 和与 REAC 技术结合的 HA 结合蛋白形成了一个有趣的网络，作用于细胞极性和细胞内环境的调节。这表明 REAC 技术在干细胞调节的细胞内生态位水平上是有效的。
