14-3-3σ controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway
14-3-3σ controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway
复制标题
DOI：
10.1016/j.bbrc.2010.01.084
复制
发表时间：
2010-02-19
影响因子：
3.1
通讯作者：
Li, Qiutang
中科院分区：
文献类型：
--
作者：
Xin, Ying;Lu, Qingxian;Li, Qiutang
14-3-3 sigma（也称为stratifin）在层状鳞状上皮中特异性表达，其功能最近被证明与皮肤表皮的分层和分化有关。本研究探讨了其在角膜上皮细胞增殖和分化中的作用。我们发现，重复脱毛（Er）突变小鼠的14-3-3 sigma突变导致显性负截断蛋白。表达显性负蛋白的原代角膜上皮细胞不能经历高钙诱导的细胞周期阻滞和分化。我们进一步证明，通过过表达显性负14-3-3 sigma来阻断内源性14-3-3 sigma在角膜上皮细胞中的活性，导致Notch活性和Notch1/2转录降低。值得注意的是，在14-3-3 sigma突变表达的角膜上皮细胞中，细胞内活性Notch结构域的表达克服了上皮细胞分化的障碍。我们得出结论，14-3-3 sigma通过调节Notch信号活性，在调节角膜上皮细胞增殖和分化中起关键作用。Elsevier Inc.出版。
14-3-3 sigma (also called stratifin) is specifically expressed in the stratified squamous epithelium and its function was recently shown to be linked to epidermal stratification and differentiation in the skin. In this study, we investigated its role in corneal epithelium cell proliferation and differentiation. We showed that the 14-3-3 sigma mutation in repeated epilation (Er) mutant mice results in a dominant negative truncated protein. Primary corneal epithelial cells expressing the dominant negative protein failed to undergo high calcium-induced cell cycle arrest and differentiation. We further demonstrated that blocking endogenous 14-3-3 sigma activity in corneal epithelial cells by overexpressing dominative negative 14-3-3 sigma led to reduced Notch activity and Notch1/2 transcription. Significantly, expression of the active Notch intracellular domain overcame the block in epithelial cell differentiation in 14-3-3 sigma mutant-expressing corneal epithelial cells. We conclude that 14-3-3 sigma is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity. Published by Elsevier Inc.