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Inhibition of CD95-Mediated Apoptosis through β1 Integrin in the HSG Epithelial Cell Line

机译:通过HSG上皮细胞系中的β1整合素抑制CD95介导的细胞凋亡。

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The HSG cell line serves as a model for salivary gland epithelial progenitor cell differentiation. In order for a progenitor cell to differentiate, the cell must maintain viability within its niche. Studies were designed to elucidate the mechanism for integrin-mediated HSG cell survival. HSG cells, grown on Matrigel, were resistant to CD95-mediated apoptosis. Western blot analysis showed that Matrigel induced the expression of bcl-2, bcl-xL, p63, and ΔNp63. This induction occurred by as early as 2 hrs and remained for 24 hrs. CD95-mediated apoptosis resistance was dependent, however, upon the expression of the bcl-2 family. Furthermore, Matrigel induced bcl-2 family expression was dependent on the transactivation of the EGF receptor pathway since PD98059 and AG1478 inhibited Matrigel induced bcl-2 family expression and caused HSG cells to be sensitive to CD95-mediated apoptosis. Activation of the EGF receptor pathway, by itself, however, was not sufficient to inhibit apoptosis. Blocking antibody showed that bcl-2 family expression was mediated through β1 integrin. These studies show that salivary progenitor epithelial cell survival is integrin dependent and involves the transactivation of the EGF receptor pathway.
机译:HSG细胞系可作为唾液腺上皮祖细胞分化的模型。为了使祖细胞分化,该细胞必须在其适当位置保持活力。设计研究以阐明整联蛋白介导的HSG细胞存活的机制。在Matrigel上生长的HSG细胞对CD95介导的细胞凋亡具有抗性。蛋白质印迹分析表明,Matrigel诱导了bcl-2,bcl-xL,p63和ΔNp63的表达。该诱导最早在2小时之前发生,并保持24小时。但是,CD95介导的细胞凋亡抗性取决于bcl-2家族的表达。此外,Matrigel诱导的bcl-2家族表达依赖于EGF受体途径的反式激活,因为PD98059和AG1478抑制了Matrigel诱导的bcl-2家族表达并使HSG细胞对CD95介导的凋亡敏感。然而,EGF受体途径的激活本身不足以抑制细胞凋亡。阻断抗体显示bcl-2家族表达是通过β1整合素介导的。这些研究表明,唾液祖细胞上皮细胞的存活是整联蛋白依赖性的,并且涉及EGF受体途径的反式激活。

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