BMP4 signaling in NPCs upregulates Bcl-xL to promote their survival in the presence of FGF-2
BMP4 signaling in NPCs upregulates Bcl-xL to promote their survival in the presence of FGF-2
复制标题
NPC 中的 BMP4 信号传导上调 Bcl-xL，以促进其在 FGF-2 存在下的存活
DOI：
10.1016/j.bbrc.2018.01.090
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发表时间：
2018
影响因子：
3.1
通讯作者：
Ishizaki Yasuki
中科院分区：
文献类型：
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作者：
Yamamoto Hanako;Kurachi Masashi;Naruse Masae;Shibasaki Koji;Ishizaki Yasuki
我们以前报道，BMP 4不促进CD 44阳性星形胶质细胞前体细胞（APC）的增殖或分化，但大大促进其在成纤维细胞生长因子-2（FGF-2）存在下的存活。在这项研究中，我们研究了BMP 4作为一个生存因子，也为神经干/祖细胞（NPC）分离的神经节隆起的新生小鼠大脑。我们发现BMP 4促进这些细胞的存活，但不促进其增殖或分化，就像CD 44阳性APC的情况一样。微阵列分析揭示了BMP 4下游信号通路中的一些候选分子。其中，Id 1（inhibitor of DNA-binding 1）和Bcl-xL是本研究的重点。这两个基因的表达在BMP 4的存在下被促进，并且这种促进被dorsomorphin（一种BMP 4信号传导的抑制剂）降低。此外，在BMP 4存在下，线粒体的细胞色素释放显著减少，表明BMP 4上调Bcl-xL活性。Id 1 siRNA可抑制Bcl-xL的表达，并抑制BMP 4的促生存作用。这些数据表明，BMP 4通过BMP 4-Smad 1/5/8-Id 1信号转导增强Bcl-xL的抗凋亡功能来促进NPC的存活。
We previously reported that BMP4 does not promote proliferation or differentiation of CD44-positive astrocyte precursor cells (APCs) but greatly promotes their survival in the presence of fibroblast growth factor-2 (FGF-2). In this study, we examined if BMP4 acts as a survival factor also for neural stem/progenitor cells (NPCs) isolated from ganglionic eminence of neonatal mouse brain. We found BMP4 promotes survival but not proliferation or differentiation of these cells, just as in the case for CD44-positive APCs. Microarray analysis revealed some candidate molecules in the signaling pathway downstream of BMP4. Among them, we focused on Id1 (inhibitor of DNA-binding 1) and Bcl-xL in this study. Expression of both genes was promoted in the presence of BMP4, and this promotion was reduced by dorsomorphin, an inhibitor of BMP4 signaling. Furthermore, cytochromecrelease from mitochondria was significantly reduced in the presence of BMP4, suggesting up-regulation of Bcl-xL activity by BMP4. Id1 siRNA reduced the expression of Bcl-xL, and negated survival promoting effect of BMP4. These data suggest that BMP4 promotes survival of NPCs by enhancing the anti-apoptotic function of Bcl-xL via BMP4-Smad1/5/8-Id1 signaling.