Nincheri P, Luciani P, Squecco R, Donati C, Bernacchioni C, Borgognoni L, Luciani G, Benvenuti S, Francini F, Bruni P
Department of Biochemical Sciences, University of Florence, Viale G. B. Morgagni 50, 50134, Florence, Italy.
Cell Mol Life Sci. 2009 May;66(10):1741-54. doi: 10.1007/s00018-009-9181-8.
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid which regulates multiple biological parameters in a number of cell types, including stem cells. Here we report, for the first time, that S1P dose-dependently stimulates differentiation of adipose tissue-derived mesenchymal stem cells (ASMC) towards smooth muscle cells. Indeed, S1P not only induced the expression of smooth muscle cell-specific proteins such as alpha-smooth muscle actin (alpha SMA) and transgelin, but also profoundly affected ASMC morphology by enhancing cytoskeletal F-actin assembly, which incorporated alpha SMA. More importantly, S1P challenge was responsible for the functional appearance of Ca(2+) currents, characteristic of differentiated excitable cells such as smooth muscle cells. By employing various agonists and antagonists to inhibit S1P receptor subtypes, S1P(2) turned out to be critical for the pro-differentiating effect of S1P, while S1P(3) appeared to play a secondary role. This study individuates an important role of S1P in AMSC which can be exploited to favour vascular regeneration.
1-磷酸鞘氨醇（S1P）是一种生物活性鞘脂，可调节包括干细胞在内的多种细胞类型中的多个生物学参数。在此，我们首次报道S1P以剂量依赖的方式刺激脂肪组织来源的间充质干细胞（ASMC）向平滑肌细胞分化。事实上，S1P不仅诱导了平滑肌细胞特异性蛋白如α-平滑肌肌动蛋白（α-SMA）和转胶蛋白的表达，还通过增强整合了α-SMA的细胞骨架F-肌动蛋白组装，深刻影响了ASMC的形态。更重要的是，S1P刺激导致了Ca（2+）电流的功能性出现，这是平滑肌细胞等分化的可兴奋细胞的特征。通过使用各种激动剂和拮抗剂抑制S1P受体亚型，结果表明S1P（2）对S1P的促分化作用至关重要，而S1P（3）似乎起次要作用。这项研究确定了S1P在AMSC中的重要作用，可利用这一作用促进血管再生。
