全反式维甲酸促鼠胚神经干细胞向神经元分化中BMP-2的表达及意义
钟德君, 李森, 康敏, 徐双, 魏书一, 王清, 王松
中国临床解剖学杂志 ›› 2012, Vol. 30 ›› Issue (4) : 426-430.
全反式维甲酸促鼠胚神经干细胞向神经元分化中BMP-2的表达及意义
Expression and significance of BMP-2 during rat NSCs induced by ATRA differentiating into neurons in vitro
目的 探讨全反式维甲酸(all-trans-retinoic-acid, ATRA)体外促NSCs分化为神经元的过程中,BMP-2表达的变化及意义。 方法 1.0 μmol/L ATRA诱导体外培养的鼠胚神经干细胞,诱导3、5、7、 9 d后,采用免疫细胞化学、qPCR、Western-Blot检测BMP-2表达变化。 结果 无ATRA干预时BMP-2表达量较高,随着诱导时间的延长,BMP-2表达逐渐降低,分化7~9 d时表达最低。 结论 BMP-2在 NSCs体外分化的的早期表达较高,在NSCs分化为神经元过程中逐渐下调,表明ATRA诱导NSCs向神经元的分化与BMP-2信号的抑制有关。
Objective To explore the expression and effect of BMP-2 during the rat embryonic stem cells(NSCs) induced by all-trans-retinoic acid(ATRA)differentiating into neurons in vitro. Methods The rat embryonic neural stem cells were differentially induced with 1.0 μmol/L ATRA in vitro. The expression of BMP-2 was respectively investigated by immunocytochemistry, real-time PCR and western blot at the time of inducing 3d, 5d, 7d and 9d, and compared with that of untreated cells in control group. Results The highest expression of BMP-2 was at the time of inducing 3d, and then it decreased from inducing 5d following the NSCs differentiating. There was no significant difference between 7d and 9d groups. Conclusions The expression of BMP-2 decreases in the progress of NSCS differentiating into neurons in vitro, which indicate that, the inhibition of BMP2 signal pathway participate the differentiation process of NSCs.
神经干细胞 / 全反式维甲酸 /   / BMP-2 / 分化 / 表达
Neural stem cells / All-trans-retinoic acid / BMP-2 / Differentiation / Expression
[1] Martin HM, Thomas GH, David MP, et a1. BMP2 and FGF2 cooperate to induce neural-crest-like fates from fetal and adult CNS stem cells
[J]. J. Cell Sci., 2005,118(24):5849-5860.
[2] Castranio T, Mishina Y. Bmp2 is required for cephalic neural tube closure in the mouse
[J]. Dev Dyn, 2009, 238(1):110-122..
[3] 钟德君, 张德胜, 宋跃明. 全反式维甲酸对鼠胚神经干细胞增殖和分化的作用
[J]. 中国修复重建外科杂志, 2008,22(2):206-211.
[4] 钟德君, 张德胜, 宋跃明. 鼠胚神经干细胞体外培养方法的优化
[J]. 中国组织工程研究与临床康复, 2007,11(50):10088-10092.
[5] Doe CQ. Neural stem cells: balancing self-renewal with differentiation
[J]. Development, 2008, 135(1): 1575 - 1587.
[6] Jacobs S, Lie DC, DeCicco KL, et a1. Retinoic acid is required early during adult neurogenesis in the dentate gyrus
[J]. PNAS, 2006, 103(10): 3902 -3907.
[7] Maden M. Retinoid signalling in the development of the central nervous system
[J]. Nat Rev Neurosci, 2002, 3(11): 843-853.
[8] Miyazono K, Kamiya Y, Morikawa M, et a1. Bone morphogenetic protein receptors and signal transduction
[J]. J. Biochem., 2010,147(1): 35-51.
[9] Aida DG, Margarida S, Stuckey DW, et a1. BMP signalling inhibits premature neural differentiation in the mouse embryo
[J]. Development, 2007, 134(18): 3359-3369.
[10] Marchal L, Luxardi G, Thomé V, et a1. BMP inhibition initiates neural induction via FGF signaling and Zic genes
[J]. PNAS, 2009, 106(41): 17437-17442.
[11] Moustakas A.Smad signalling network
[J]. J. Cell Sci., 2002, 115(17): 3355-3356.
[12] Sakuta H, Takahashi H, Shintani T, et a1. Role of Bone Morphogenic Protein 2 in Retinal Patterning and Retinotectal Projection
[J]. J. Neurosci, 2006, 26(42): 10868 - 10878
[13] Doss MX, Chen S, Winkler J, et a1. Transeriptomie and phenotypic analysis of murine embryonic stem cell derived BMP2+ lineage cells:an insight into mesodermal patterning
[J]. Genome Biol, 2007, 8(9):R184.
[14] Miyazono K. TGF-beta signaling by Smad proteins
[J]. Cytokine Growth Factor Rev, 2000, 11(1.2):15-22.
[15] 张治元, 杨 辉, 刘仕勇,等. BMP2在SVZa神经干细胞向神经元分化中的作用
[J].第三军医大学学报, 2003, 25(20):1788-1791.
[16] 钟德君, 康敏, 王清, 等. Wnt-1在全反式维甲酸促鼠胚神经干细胞向神经元分化中的作用
[J]. 中国修复重建外科杂志, 2009,23(6):43-47.
[17] Kasai M, Satoh K, Akiyama T. Wnt signaling regulates the sequential onset of neurogenesis and gliogenesis via induction of BMPs
[J]. Genes Cells, 2005,10(8):777-783.
泸州市重点科技计划项目(2008-23-5); 四川省卫生厅科研项目(2008-527-080178)
/
〈 |
|
〉 |