Liver X receptors agonist promotes differentiation of rat bone marrow derived mesenchymal stem cells into dopaminergic neuron-like cells.
Liver X receptors agonist promotes differentiation of rat bone marrow derived mesenchymal stem cells into dopaminergic neuron-like cells.
复制标题
肝脏X受体激动剂促进大鼠骨髓间充质干细胞分化为多巴胺能神经元样细胞
DOI：
10.18632/oncotarget.23076
复制
发表时间：
2018-01-02
期刊：
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Cheng O;Tian X;Luo Y;Mai S;Yang Y;Kuang S;Chen Q;Ma J;Chen B;Li R;Yang L;Li H;Hu C;Zhang J;Chen Z;Li Y;Xia H;Xu Y;Yang J
从骨髓间充质干细胞（BMSCs）分化的多巴胺（DA）能神经元可能是帕金森病细胞替代治疗的一个有价值的来源。最近的研究表明，LXR及其配体的新功能已被提出，以防止在成人神经系统中的PD。本研究旨在观察肝X受体激动剂对大鼠骨髓间充质干细胞向多巴胺能神经元分化的影响。免疫细胞化学法检测神经元标志物Tuj 1和Nestin、DA能神经元特异性标志物酪氨酸羟化酶（tyrosine hydroxylase，TH）、LXR α和LXR β的表达，定量细胞计数法检测TH/Tuj 1阳性细胞。qPCR检测LXR α、LXR β、TH、DAT、Nurr 1、Pitx 3、En 1和Lmx 1b的mRNA表达。与生长因子（growth factors，GF）组相比，LXR和GF联合诱导大鼠BMSCs向TH表达细胞分化的有效率为87.42%，诱导周期为6d。单独的LXR激动剂不诱导分化。与单用GF相比，LXR和GF联合应用可增加LXR α和LXR β蛋白和mRNA的表达，增加TH、DAT、Nurr 1和Pitx 3 mRNA的表达，降低En 1和Lmx 1b mRNA的表达。我们的实验结果表明，LXR激活导致提高诱导效率，并通过调节DA发育相关基因的表达，缩短大鼠BMSCs向DA神经元样细胞的诱导期，LXR可以被认为是一个候选的药物开发的目标，以促进BMSCs向DA神经元分化。
Dopaminergic (DA) neurons derived from bone marrow derived mesenchymal stem cells (BMSCs) maybe a valuable source for cell replacement therapy in Parkinson disease. Recent studies showed that new functions of LXR and their ligands have been proposed to prevent PD in the adult nervous system. The present study was designed to observe the effect of liver X receptors (LXR) agonist on differentiation of rat BMSCs into DA neurons. Expressions of the neuronal markers (Tuj1 and Nestin), the specific marker of DA neurons (tyrosine hydroxylase, TH), LXR α and LXR β were measured by immunocytochemical assay and TH/Tuj1 positive cells were determined by quantitative cell count analyses. mRNA expressions of LXR α, LXR β, TH, DAT, Nurr1, Pitx3, En1 and Lmx1b were measured by qPCR. Compared with growth factors (GF) treated group, combined use of LXR and GF induced rat BMSCs to TH-expressing cells with 87.42% of efficiency in 6 days of period of induction. LXR agonist alone did not induce the differentiation. Compared with GF alone, combined use of LXR and GF increased expressions of LXR α and LXR β protein and mRNA and TH, DAT, Nurr1, and Pitx3 mRNA, decreased expressions of En1 and Lmx1b mRNA. Our experimental results indicated that LXR activation leads to improve induction efficiency and shorten induction period of rat BMSCs into DA neuron-like cells through regulating DA development-related genes expressions and that LXR can be considered as a candidate target for drug development to improve differentiation of BMSCs into DA neurons.
登录
查看更多内容
影响因子：
--
作者：
Fu MH;Li CL;Lin HL;Chen PC;Calkins MJ;Chang YF;Cheng PH;Yang SH
通讯作者：
Yang SH
影响因子：
6
作者：
Poewe, Werner
通讯作者：
Poewe, Werner
影响因子：
3.7
作者：
Cui H;Zhu Y;Jiang D
通讯作者：
Jiang D
DOI：
10.1007/s11626-013-9701-6
发表时间：
2014-04-01
影响因子：
2.1
作者：
Fan, Lixing;Hu, Kaimeng;Liu, Houqi
通讯作者：
Liu, Houqi
影响因子：
4
作者：
Barzilay, Ran;Ben-Zur, Tali;Offen, Daniel
通讯作者：
Offen, Daniel