Tgf-β-mediated FasL-Fas-Caspase Pathway Is Crucial during Palatogenesis
Tgf-β-mediated FasL-Fas-Caspase Pathway Is Crucial during Palatogenesis
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DOI：
10.1177/0022034511408613
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发表时间：
2011-08-01
影响因子：
7.6
通讯作者：
Chai, Y.
中科院分区：
文献类型：
--
作者：
Huang, X.;Yokota, T.;Chai, Y.
细胞程序性死亡或细胞凋亡是腭融合过程中内侧缘上皮（MEE）的命运之一。转化生长因子β（TGF-β）信号传导（如TGF-β 3）是凋亡消失所必需的，但TGF-β 3与凋亡之间的关系仍不清楚。在这里，我们表明Fas配体（FasL）-Fas-半胱天冬酶外源性凋亡途径在野生型小鼠的腭融合过程中发挥作用，但在缺乏Tgf-β 3（Tgf-β 3（-/-））或Tgf β r2的小鼠中检测不到（K14-Cre; Tgfbr 2（fl/fl））。在腭器官培养过程中，抑制FasL-Fas系统导致中线上皮缝（MES）的持续存在和半胱天冬酶活性的抑制。此外，异位FasL蛋白诱导K14-Cre; Tgfbr 2（fl/fl）小鼠MES的凋亡。因此，我们得出结论，Fas L-Fas-caspase外源性凋亡途径是由TGF-β 3信号级联调节，是必不可少的腭融合在颅面发育。
Programmed cell death, or apoptosis, is one of the fates of the medial edge epithelium (MEE) during palatal fusion. Transforming growth factor beta (Tgf-beta) signaling (such as Tgf-beta 3) is required for the disappearance of the MEE, but the relationship between Tgf-beta 3 and apoptosis remains unclear. Here we show that the Fas ligand (FasL)-Fas-Caspase extrinsic apoptosis pathway functions during palatal fusion in wild-type mice, but is not detectable in mice lacking Tgf-beta 3 (Tgf-beta 3(-/-)) or Tgf beta r2 in the MEE (K14-Cre; Tgfbr2(fl/fl)). Inhibition of the FasL-Fas system results in persistence of the midline epithelial seam (MES) and inhibition of caspase activity during palatal organ culture. Moreover, ectopic FasL protein induces apoptosis in MES of K14-Cre; Tgfbr2(fl/fl) mice. Thus, we conclude that the FasL-Fas-caspase extrinsic apoptosis pathway is regulated by the Tgf-beta 3 signaling cascade and is essential for palatal fusion during craniofacial development.