Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
复制标题
DOI：
10.1371/journal.pone.0020389
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bruni P
中科院分区：
文献类型：
--
作者：
Donati C;Marseglia G;Magi A;Serratì S;Cencetti F;Bernacchioni C;Nannetti G;Benelli M;Brunelli S;Torricelli F;Cossu G;Bruni P
不同的细胞可以通过分化成平滑肌（SM）细胞来促进血管损伤后的修复;然而，目前所涉及的细胞外信号的特征尚不清楚。中胚层成血管细胞是能够分化成各种中胚层细胞类型（包括SM细胞）的祖细胞。在这项研究中，多效鞘脂鞘氨醇1-磷酸（S1 P）在人mesoangioblast的生物学作用已初步研究了基因芯片分析。获得的数据证实了这种鞘脂的抗凋亡作用，并首次确定了对SM细胞的强烈分化作用。定量mRNA和蛋白质分析证实了微阵列的结果，表明增强的肌原性标志物蛋白的表达和转录因子GATA 6及其共调节因子LMCD 1的表达的调节。更重要的是，S1 P诱导的GATA 6上调是导致SM特异性收缩蛋白表达增强的原因。此外，通过特异性基因沉默实验，GATA 6在细胞因子TGFβ的促分化活性中是关键的。最后，响应于TGFβ的内源性S1 P形成的药理学抑制消除了GATA 6的上调，支持了S1 P途径在介导TGFβ的促肌生成作用中起生理作用的观点。这项研究个性化GATA 6作为新的球员在复杂的转录调控mesoangioblast分化为SM细胞，并强调了S1 P的作用，有利于血管再生。
Different cells can contribute to repair following vascular injury by differentiating into smooth muscle (SM) cells; however the extracellular signals involved are presently poorly characterized. Mesoangioblasts are progenitor cells capable of differentiating into various mesoderm cell types including SM cells. In this study the biological action exerted by the pleiotropic sphingolipid sphingosine 1-phosphate (S1P) in human mesoangioblasts has been initially investigated by cDNA microarray analysis. Obtained data confirmed the anti-apoptotic action of this sphingolipid and identified for the first time a strong differentiating action toward SM cells. Quantitative mRNA and protein analysis corroborated the microarray results demonstrating enhanced expression of myogenic marker proteins and regulation of the expression of transcription factor GATA6 and its co-regulator, LMCD1. Importantly, GATA6 up-regulation induced by S1P was responsible for the enhanced expression of SM-specific contractile proteins. Moreover, by specific gene silencing experiments GATA6 was critical in the pro-differentiating activity of the cytokine TGFβ. Finally, the pharmacological inhibition of endogenous S1P formation in response to TGFβ abrogated GATA6 up-regulation, supporting the view that the S1P pathway plays a physiological role in mediating the pro-myogenic effect of TGFβ. This study individuates GATA6 as novel player in the complex transcriptional regulation of mesoangioblast differentiation into SM cells and highlights a role for S1P to favour vascular regeneration.
登录
查看更多内容
DOI：
10.1161/atvbaha.109.191965
发表时间：
2009-10
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Grabski AD;Shimizu T;Deou J;Mahoney WM Jr;Reidy MA;Daum G
通讯作者：
Daum G
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
30.8
作者：
Bergamaschi, Daniele;Samuels, Yardena;Lu, Xin
通讯作者：
Lu, Xin
DOI：
10.1073/pnas.0603386103
发表时间：
2006-11-07
影响因子：
11.1
作者：
Morosetti, Roberta;Mirabella, Massimiliano;Cossu, Giulio
通讯作者：
Cossu, Giulio
影响因子：
4.8
作者：
Donati, C;Meacci, E;Bruni, P
通讯作者：
Bruni, P