TGFbeta1 induces Jagged1 expression in astrocytes via ALK5 and Smad3 and regulates the balance between oligodendrocyte progenitor proliferation and differentiation.
TGFbeta1 induces Jagged1 expression in astrocytes via ALK5 and Smad3 and regulates the balance between oligodendrocyte progenitor proliferation and differentiation.
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DOI：
10.1002/glia.20978
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发表时间：
2010-06
期刊：
影响因子：
6.2
通讯作者：
John, Gareth R.
中科院分区：
文献类型：
--
作者：
Zhang, Yueting;Zhang, Jingya;Navrazhina, Kristina;Argaw, Azeb Tadesse;Zameer, Andleeb;Gurfein, Blake T.;Brosnan, Celia F.;John, Gareth R.
Notch 1受体信号调节发育中的少突胶质细胞祖细胞分化和髓鞘形成，以及成年CNS中的髓鞘再生。在活动性多发性硬化病变中，Notch 1定位于少突胶质细胞谱系细胞，其配体Jagged 1由反应性星形胶质细胞表达。在这里，我们研究了人类星形胶质细胞中Jagged 1的诱导及其对少突胶质细胞分化的影响。在人星形胶质细胞培养物中，细胞因子TGFβ1诱导Jagged 1表达，阻断TGFβ1受体激酶ALK 5可消除Jagged 1诱导。TGFβ2和β3具有相似的作用，但在对TGFβ家族成员激活素A或其他细胞因子的反应中未观察到诱导。在下游，TGFβ1激活Smad依赖性信号传导，以及包括PI 3激酶、p38和JNK MAP激酶的Smad非依赖性通路，但只有抑制Smad依赖性通路才能阻断Jagged 1的表达。siRNA抑制Smad 3下调Jagged 1的诱导，这是由Smad 2 siRNA增强。用Notch 1胞内信号结构域核转染的纯化的少突胶质祖细胞（OPCs）以分化为代价显示出向增殖的转变，证明了Notch 1信号在OPCs中的功能相关性。此外，人OPCs接种到Jagged 1表达星形胶质细胞表现出有限的分化。总的来说，这些数据说明了人类星形胶质细胞中Jagged 1诱导的潜在机制，并表明TGFβ1诱导的Jagged 1-Notch 1信号转导激活可能影响人类CNS中OPC池的大小和分化。
Notch1 receptor signaling regulates oligodendrocyte progenitor differentiation and myelin formation in development, and during remyelination in the adult CNS. In active multiple sclerosis lesions, Notch1 localizes to oligodendrocyte lineage cells, and its ligand Jagged1 is expressed by reactive astrocytes. Here, we examined induction of Jagged1 in human astrocytes, and its impact on oligodendrocyte differentiation. In human astrocyte cultures, the cytokine TGFβ1 induced Jagged1 expression, and blockade of the TGFβ1 receptor kinase ALK5 abrogated Jagged1 induction. TGFβ2 and β3 had similar effects, but induction was not observed in response to the TGFβ family member activin A or other cytokines. Downstream, TGFβ1 activated Smad-dependent signaling, and Smad-independent pathways that included PI3 kinase, p38 and JNK MAP kinase, but only inhibition of the Smad-dependent pathway blocked Jagged1 expression. SiRNA inhibition of Smad3 downregulated induction of Jagged1, and this was potentiated by Smad2 siRNA. Purified oligodendrocyte progenitor cells (OPCs) nucleofected with Notch1 intracellular signaling domain displayed a shift towards proliferation at the expense of differentiation, demonstrating functional relevance of Notch1 signaling in OPCs. Furthermore, human OPCs plated onto Jagged1-expressing astrocytes exhibited restricted differentiation. Collectively, these data illustrate the mechanisms underlying Jagged1 induction in human astrocytes, and suggest that TGFβ1-induced activation of Jagged1-Notch1 signaling may impact the size and differentiation of the OPC pool in the human CNS.
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影响因子：
2.9
作者：
ABE, M;HARPEL, JG;RIFKIN, DB
通讯作者：
RIFKIN, DB
影响因子：
12.7
作者：
Seifert, Thomas;Bauer, Jan;Storch, Maria K.
通讯作者：
Storch, Maria K.
NOTCH1控制脊髓中的少突胶质细胞分化。
影响因子：
7.8
作者：
Genoud, Stephane;Lappe-Siefke, Corinna;Goebbels, Sandra;Radtke, Freddy;Aguet, Michel;Scherer, Steven S;Suter, Ueli;Nave, Klaus-Armin;Mantei, Ned
通讯作者：
Mantei, Ned
影响因子：
30.8
作者：
Li, LH;Krantz, ID;Spinner, NB
通讯作者：
Spinner, NB
Notch 和 TGF-β 信号通路之间的串扰由 Notch 胞内结构域与 Smad3 的相互作用介导。
影响因子：
7.8
作者：
Blokzijl, A;Dahlqvist, C;Reissmann, E;Falk, A;Moliner, A;Lendahl, U;Ibáñez, CF
通讯作者：
Ibáñez, CF