A mechanistic study of Toxoplasma gondii ROP18 inhibiting differentiation of C17.2 neural stem cells.
A mechanistic study of Toxoplasma gondii ROP18 inhibiting differentiation of C17.2 neural stem cells.
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弓形虫ROP18抑制C17.2神经干细胞分化的机制研究
DOI：
10.1186/s13071-017-2529-2
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发表时间：
2017-11-23
影响因子：
3.2
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Zhang X;Su R;Cheng Z;Zhu W;Li Y;Wang Y;Du J;Cai Y;Luo Q;Shen J;Yu L
研究背景先天性弓形虫感染是导致出生缺陷的重要因素。神经干细胞（NSC）被发现是脑发育过程中寄生虫的靶细胞之一。ROP 18作为寄生虫的一个关键毒力因子，通过特异性结合不同的宿主免疫相关分子，介导宿主先天性和适应性免疫应答的抑制。然而，它的致病作用，在神经干细胞仍然habitu.ResultsIn本研究中，ROP 18重组腺病毒（Ad-ROP 18）的构建和感染C17.2神经干细胞。在分化培养基中培养3d或5d后，检测C17. 2神经干细胞的分化情况和Wnt/β-catenin信号通路的活性。结果显示，ROP 18基因转染的C17. 2神经干细胞中神经元标志物β III-微管蛋白的蛋白水平显著降低，表明ROP 18基因抑制了C17. 2神经干细胞的分化。转染ROP 18基因的C17. 2神经干细胞中β-catenin水平低于Ad组。此外，与Ad组相比，Ad-ROP 18转染的C17. 2 NSC中的神经生成素1（Ngn 1）和神经生成素2（Ngn 2）显著下调（P 0. 05）。TOP flash/FOP flash双荧光素酶报告系统显示，转染Ad-ROP 18后，C17. 2神经干细胞Wnt/β-catenin通路活性明显降低。
BackgroundCongenital infection of Toxoplasma gondii is an important factor causing birth defects. The neural stem cells (NSCs) are found to be one of the target cells for the parasite during development of the brain. As a key virulence factor of the parasite that hijacks host cellular functions, ROP18 has been demonstrated to mediate the inhibition of host innate and adaptive immune responses through specific binding different host immunity related molecules. However, its pathogenic actions in NSCs remain elusive.ResultsIn the present study, ROP18 recombinant adenovirus (Ad-ROP18) was constructed and used to infect C17.2 NSCs. After 3d- or 5d–culture in differentiation medium, the differentiation of C17.2 NSCs and the activity of the Wnt/β-catenin signaling pathway were detected. The results showed that the protein level of βIII-tubulin, a marker of neurons, in the Ad-ROP18-transfected C17.2 NSCs was significantly decreased, indicating that the differentiation of C17.2 NSCs was inhibited by the ROP18. The β-catenin level in the Ad-ROP18-transfected C17.2 NSCs was found to be lower than that in the Ad group. Also, neurogenin1 (Ngn1) and neurogenin2 (Ngn2) were downregulated significantly (P < 0.05) in the Ad-ROP18-transfected C17.2 NSCs compared to the Ad group. Accordingly, the TOP flash/FOP flash dual-luciferase report system showed that the transfection of Ad-ROP18 decreased the Wnt/β-catenin pathway activity in the C17.2 NSCs.Conclusions The findings help to better understand potential mechanisms of brain pathology induced by TgROP18.
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影响因子：
3.4
作者：
Khaminets A;Hunn JP;Könen-Waisman S;Zhao YO;Preukschat D;Coers J;Boyle JP;Ong YC;Boothroyd JC;Reichmann G;Howard JC
通讯作者：
Howard JC
影响因子：
56.9
作者：
Saeij, J. P. J.;Boyle, J. P.;Boothroyd, J. C.
通讯作者：
Boothroyd, J. C.
影响因子：
3.1
作者：
LaBarre, DD;Lowy, RJ
通讯作者：
Lowy, RJ
影响因子：
14.2
作者：
Hill, D;Dubey, JP
通讯作者：
Dubey, JP
大鼠巨细胞病毒对早期大鼠胚胎神经系统的影响
影响因子：
5.5
作者：
Sun, Xiuning;Guan, YingJun;Liu, Zhijun
通讯作者：
Liu, Zhijun