Meteorin promotes the formation of GFAP-positive glia via activation of the Jak-STAT3 pathway
Meteorin promotes the formation of GFAP-positive glia via activation of the Jak-STAT3 pathway
复制标题
DOI：
10.1242/jcs.063784
复制
发表时间：
2010-06-01
影响因子：
4
通讯作者：
Kim, Kyu-Won
中科院分区：
文献类型：
--
作者：
Lee, Hye Shin;Han, Jiyeon;Kim, Kyu-Won
镍纹蛋白是一种孤儿配体，先前已报道其控制神经突发生和血管生成以及神经胶质细胞生成。然而，这种因子在CNS发育中的确切功能和潜在的分子机制知之甚少。在这里，我们表明，meteorin参与GFAP阳性胶质细胞分化通过激活Jak-STAT 3通路，通过使用神经球和视网膜外植体培养系统。在胚胎脑发育过程中，meteorin是高度表达的神经干细胞和放射状胶质细胞的脑室区和脑室区以外的未成熟神经元，但其表达消失自发的发展进行中，除了GFAP阳性星形胶质细胞。在培养的神经球中，流星蛋白激活STAT 3，进而通过增强STAT 3与启动子的结合来增加GFAP的转录活性。通过meteorin刺激，分化中的神经球显示出GFAP阳性细胞数量的增加，但是通过使用Jak抑制剂或STAT 3 siRNA阻断Jak-STAT 3通路，该效果被消除。此外，我们扩大我们的研究结果的视网膜，并表明，陨石增加GFAP的表达在穆勒神经胶质细胞。总之，我们的研究结果表明，meteorin促进GFAP阳性胶质细胞的形成，通过介导的Jak-STAT 3信号通路在皮质干细胞分化和视网膜胶质细胞的发展。
Meteorin is an orphan ligand which has been previously reported to control neuritogenesis and angiogenesis, as well as gliogenesis. However, the precise function of this factor in CNS development and the underlying molecular mechanisms are poorly understood. Here, we demonstrate that meteorin is involved in GFAP-positive glial differentiation through activation of the Jak-STAT3 pathway, by using neurosphere and retinal explant culture systems. During embryonic brain development, meteorin is highly expressed in neural stem and radial glia cells of the ventricular zone and immature neurons outside the ventricular zone but its expression disappears spontaneously as development proceeds except in GFAP-positive astrocytes. In cultured neurospheres, meteorin activates STAT3, and in turn increases the transcriptional activity of GFAP by enhancing the binding of STAT3 to the promoter. By meteorin stimulation, differentiating neurospheres show increased numbers of GFAP-positive cells, but the effect is abrogated by a blockade of the Jak-STAT3 pathway using either a Jak inhibitor or STAT3 siRNA. Furthermore, we expand our findings to the retina, and show that meteorin increases GFAP expression in Muller glia. Together, our results suggest that meteorin promotes GFAP-positive glia formation by mediating the Jak-STAT3 signaling pathway during both cortical stem cell differentiation and retinal glia development.