Notch signaling regulates cell density-dependent apoptosis of NIH 3T3 through an IL-6/STAT3 dependent mechanism.
Notch signaling regulates cell density-dependent apoptosis of NIH 3T3 through an IL-6/STAT3 dependent mechanism.
复制标题
DOI：
10.1016/j.ejcb.2018.09.001
复制
发表时间：
2018-09
影响因子：
6.6
通讯作者：
Hogaboam CM
中科院分区：
文献类型：
--
作者：
Matsuno Y;Kiwamoto T;Morishima Y;Ishii Y;Hizawa N;Hogaboam CM
细胞凋亡是维持细胞内环境稳定的重要生理过程。以前的报道已经证明，细胞以细胞密度依赖性的方式经历凋亡，其部分受信号转导和转录激活因子（STAT）3的调节。然而，调节细胞密度依赖性凋亡的分子机制迄今尚未得到彻底研究。由于Notch信号是通过直接的细胞与细胞接触激活的，并在细胞命运的决定中起着关键作用，我们研究了Notch信号在小鼠胚胎成纤维细胞NIH 3 T3细胞的细胞密度依赖性凋亡中的作用。随着细胞密度的增加，IL-6的表达被诱导，这是STAT 3激活以及凋亡调节所必需的。Notch信号也以细胞密度依赖性方式被激活。通过siRNA介导的靶向Jagged 1表达或γ-分泌酶抑制剂处理阻断Notch信号传导证明Notch信号传导激活对于IL-6诱导是必需的。Notch 1胞内结构域的过表达对Notch信号传导的组成性激活足以诱导IL-6，其通过直接转录激活介导。总之，我们的研究表明，Notch信号通过IL-6/STAT 3依赖性机制调节细胞密度依赖性凋亡。因此，Notch信号通路可能是以细胞凋亡失调为特征的疾病的一个新的治疗靶点。
Apoptosis is a physiological process that plays a critical maintenance role in cellular homeostasis. Previous reports have demonstrated that cells undergo apoptosis in a cell density-dependent manner, w hich is regulated, in part, by signal transducers and activators of transcription (STAT) 3. The molecular mechanisms regulating cell density-dependent apoptosis, however, has not been thoroughly investigated to date. Since Notch signaling is activated via direct cell-to-cell contact and plays a pivotal role in cell fate decisions, we examined the role of Notch signaling in cell density-dependent apoptosis of mouse embryonic fibroblasts NIH 3T3 cells. With the increase in cell density, IL-6 expression was induced, which was necessary for STAT 3 activation as well as apoptosis regulation. Notch signaling was also activated in a cell-density dependent manner. Blocking Notch signaling either through siRNA-mediated targeting of Jagged1 expression or γ-secretase inhibitor treatment demonstrated that Notch signaling activation was necessary for IL-6 induction. Constitutive activation of Notch signaling via the overexpression of Notch1 intracellular domain was sufficient for the induction of IL-6, which was mediated via direct transcriptional activation. Taken together, our study indicates that Notch signaling regulates cell density-dependent apoptosis through IL-6/STAT3-dependent mechanism. Consequently, Notch signaling might represent an ovel therapeutic target in diseases characterized by dysregulated apoptosis.
登录
查看更多内容
影响因子：
14.9
作者：
Palmieri, M;Sasso, MP;Furia, A
通讯作者：
Furia, A
DOI：
10.1165/rcmb.2002-0262oc
发表时间：
2003-10-01
影响因子：
6.4
作者：
Moodley, YP;Misso, NLA;Knight, DA
通讯作者：
Knight, DA
影响因子：
21.3
作者：
Procopio MG;Laszlo C;Al Labban D;Kim DE;Bordignon P;Jo SH;Goruppi S;Menietti E;Ostano P;Ala U;Provero P;Hoetzenecker W;Neel V;Kilarski WW;Swartz MA;Brisken C;Lefort K;Dotto GP
通讯作者：
Dotto GP
影响因子：
64.5
作者：
Benedito, Rui;Roca, Cristina;Adams, Ralf H.
通讯作者：
Adams, Ralf H.
影响因子：
5.3
作者：
Noseda, M;Chang, L;Karsan, A
通讯作者：
Karsan, A