Neuropoietin induces neuroepithelial cells to differentiate into astrocytes via activation of STAT3.
Neuropoietin induces neuroepithelial cells to differentiate into astrocytes via activation of STAT3.
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DOI：
10.1016/j.cyto.2006.10.007
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发表时间：
2006-10
期刊：
影响因子：
3.8
通讯作者：
M. Ohno;J. Kohyama;M. Namihira;Tsukasa Sanosaka;J. Takahashi;N. Hashimoto;K. Nakashima
中科院分区：
文献类型：
--
作者：
M. Ohno;J. Kohyama;M. Namihira;Tsukasa Sanosaka;J. Takahashi;N. Hashimoto;K. Nakashima
神经生成素（neuropoietin，NP）是最近发现的白细胞介素（interleukin，IL）-6细胞因子家族的成员，与糖蛋白130（glycoprotein 130，gp 130）共同作为信号转导受体，在胚胎脑中高表达。在这项研究中，我们表明，NP有可能诱导神经上皮细胞分化为星形胶质细胞。NP刺激导致星形胶质细胞标志物胶质细胞酸性蛋白（GFAP）基因的启动子激活，其明显受到转录因子、信号转导子和转录激活因子3（STAT 3）的显性负性形式的表达或基因启动子内STAT 3结合元件中的核苷酸取代的抑制。我们进一步表明，NP诱导内源性STAT 3的结合，其同源序列内的gfap基因启动子在神经上皮细胞。此外，与其他IL-6细胞因子家族成员一样，NP以与骨形态发生蛋白（BMP）-2协同的方式促进星形胶质细胞分化。总之，我们的数据表明，NP可以被认为是一种新的星形胶质细胞诱导细胞因子在发育中的大脑。
Neuropoietin (NP) is a recently identified member of the interleukin (IL)-6 family of cytokines, which share glycoprotein 130 (gp130) as a signal-transducing receptor component, and is highly expressed in embryonic brain. In this study, we show that NP has the potential to induce neuroepithelial cells to differentiate into astrocytes. NP stimulation leads to promoter activation of the gene for an astrocyte marker, glial fibrillary acidic protein (GFAP), which is clearly inhibited by either expression of a dominant-negative form of a transcription factor, signal transducer and activator of transcription 3 (STAT3) or by a nucleotide-substitution in the STAT3-binding element within the gene promoter. We further show that NP induces binding of endogenous STAT3 to its cognate sequence within the gfap gene promoter in neuroepithelial cells. Moreover, like the other IL-6 cytokine family members, NP promotes astrocyte differentiation in a synergistic manner with bone-morphogenetic protein (BMP)-2. Taken together, our data indicate that NP can be considered as a new astrocyte-inducing cytokine in the developing brain.