Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russia.
Sci Rep. 2016 Sep 6;6:32835. doi: 10.1038/srep32835.
Sympathetic neurons are important components of mesenchymal stem cells (MSCs) niche and noradrenaline regulates biological activities of these cells. Here we examined the mechanisms of regulation of MSCs responsiveness to noradrenaline. Using flow cytometry, we demonstrated that α1A adrenergic receptors isoform was the most abundant in adipose tissue-derived MSCs. Using calcium imaging in single cells, we demonstrated that only 6.9 ± 0.8% of MSCs responded to noradrenaline by intracellular calcium release. Noradrenaline increases MSCs sensitivity to catecholamines in a transitory mode. Within 6 hrs after incubation with noradrenaline the proportion of cells responding by Ca(2+) release to the fresh noradrenaline addition has doubled but declined to the baseline after 24 hrs. Increased sensitivity was due to the elevated quantities of α1A-adrenergic receptors on MSCs. Such elevation depended on the stimulation of β-adrenergic receptors and adenylate cyclase activation. The data for the first time clarify mechanisms of regulation of MSCs sensitivity to noradrenaline.
交感神经元是间充质干细胞 (MSC) 生态位的重要组成部分，去甲肾上腺素调节这些细胞的生物活性。在这里，我们研究了调节 MSC 对去甲肾上腺素反应性的机制。我们通过流式细胞术证明，α1A 肾上腺素能受体亚型在脂肪组织来源的 MSC 中最为丰富。通过单细胞钙成像，我们证明只有 6.9±0.8%的 MSC 通过细胞内钙释放对去甲肾上腺素产生反应。去甲肾上腺素以瞬时方式增加 MSC 对儿茶酚胺的敏感性。在与去甲肾上腺素孵育 6 小时内，对新鲜去甲肾上腺素添加物通过 Ca(2+)释放产生反应的细胞比例增加了一倍，但在 24 小时后降至基线。敏感性增加是由于 MSC 上 α1A 肾上腺素能受体数量增加。这种增加取决于β肾上腺素能受体的刺激和腺苷酸环化酶的激活。这些数据首次阐明了调节 MSC 对去甲肾上腺素敏感性的机制。
