Vitamin A regulates neural stem cell proliferation in rats after hypoxic-ischemic brain damage via RARɑ-mediated modulation of the β-catenin pathway
Vitamin A regulates neural stem cell proliferation in rats after hypoxic-ischemic brain damage via RARɑ-mediated modulation of the β-catenin pathway
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维生素 A 通过 RARÉ 介导的 β-连环蛋白途径调节大鼠缺氧缺血性脑损伤后的神经干细胞增殖
DOI：
10.1016/j.neulet.2020.134922
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发表时间：
2020-03
影响因子：
2.5
通讯作者：
wei jiang
中科院分区：
文献类型：
--
作者：
min zhao;wei jiang
我们前期的实验发现，适当剂量的维生素A（VA）可通过与RARα结合激活PI 3 K/AKT信号通路，影响缺氧缺血性脑损伤（HIBD）后神经元的凋亡;然而，VA对HIBD后神经元的其他保护作用，如是否促进神经干细胞（NSC）增殖尚不清楚。在这项研究中，体内和体外实验表明，VA通过RAR β调节β-catenin信号传导，影响HIBD后NSC增殖并改善神经认知结果。由于神经干细胞的聚集和悬浮生长特性，我们用PC 12细胞进行体外实验来模拟神经干细胞。采用流式细胞术、CCK 8、EdU染色、免疫荧光和行为学等方法，观察维甲酸（RA）对HIBD后神经干细胞增殖和功能的影响。实时定量PCR和Western blotting检测RARα和β-catenin通路组分的表达。结果表明，VA缺乏（VAD）组的学习记忆功能损害较VA正常（货车）组严重。VAD组海马神经干细胞增殖能力较货车组明显降低。VAD组RAR β、AKT、GSK-3β、β-catenin和Cyclin D1的mRNA和蛋白表达均显著低于货车组。在体外，过高和过低的RA干预导致增殖降低，而适当的RA浓度（1 - 5 μmol/L）显著促进增殖，S期细胞和高β-catenin通路表达。结果提示，适宜浓度的VA可通过促进新生儿HIBD损伤后海马神经干细胞的增殖而发挥神经保护作用。VA激活RAR β，调节β-catenin信号通路，进而上调Cyclin D1表达，促进NSC增殖，最终发挥神经保护作用。
Our previous experiments found that a suitable dose of vitamin A (VA) can affect neuronal apoptosis after hypoxic-ischemic brain damage (HIBD) by binding to RARα to activate the PI3K/AKT signaling pathway; however, the other neuroprotective effects of VA after HIBD, for example, whether it promotes neural stem cell (NSC) proliferation, remain unclear. In this study, in vivo and in vitro experiments revealed that VA regulates β-catenin signaling through RARɑ to affect NSC proliferation after HIBD and to improve neurocognitive outcomes. Because of the accumulation and suspended growth characteristics of NSCs, we performed in vitro experiments with PC12 cells to mimic NSCs. Flow cytometry, CCK8, EdU staining, immunofluorescence and behavioral tests were performed to explore the effects of retinoic acid (RA) on NSC proliferation and post-HIBD function. The expression of RARα and β-catenin pathway components were measured by real-time PCR and Western blotting. We found that the learning and memory of the VA-deficient (VAD) group was more seriously damaged than that of the VA normal (VAN) group. The proliferation of hippocampal NSCs was significantly decreased in the VAD group compared with the VAN group. The mRNA and protein expression of RARɑ, AKT, GSK-3β, β-catenin and Cyclin D1 were significantly lower in the VAD group than in the VAN group. In vitro, too high and too low of an RA intervention resulted in decreased proliferation, while an appropriate RA concentration (1−5 μmol/L) significantly promoted proliferation, S phase cells and high β-catenin pathway expression. These results suggested that VA can exert a neuroprotective effect by promoting the proliferation of hippocampal NSCs after neonatal HIBD injury at the appropriate concentration. VA activates RARɑ, which regulates the β-catenin signaling pathway, which in turn upregulates Cyclin D1 expression, promotes NSC proliferation, and finally plays a role in the neuroprotective effect.
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影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
DOI：
10.1016/j.diff.2016.11.002
发表时间：
2017-01
期刊：
Differentiation; research in biological diversity
影响因子：
--
作者：
Mulligan WA;Wegner KA;Keil KP;Mehta V;Taketo MM;Vezina CM
通讯作者：
Vezina CM
影响因子：
6.8
作者：
Mohammed MK;Shao C;Wang J;Wei Q;Wang X;Collier Z;Tang S;Liu H;Zhang F;Huang J;Guo D;Lu M;Liu F;Liu J;Ma C;Shi LL;Athiviraham A;He TC;Lee MJ
通讯作者：
Lee MJ
影响因子：
4.2
作者：
Risa Takamura;Naoto Watamura;Miyu Nikkuni;T. Ohshima
通讯作者：
Risa Takamura;Naoto Watamura;Miyu Nikkuni;T. Ohshima
影响因子：
3.4
作者：
Zetterström, RH;Lindqvist, E;Olson, L
通讯作者：
Olson, L