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首页> 外文期刊>American Journal of Physiology >Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells.
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Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells.

机译：f-box因子foxj1在纤毛气管上皮细胞分化中的作用。

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摘要

Factors required for commitment of an undifferentiated airway epithelial cell to a ciliated cell are unknown. Cell ultrastructure analysis indicates ciliated cell commitment activates a multistage program involving synthesis of cilia precursor proteins and assembly of macromolecular complexes. Foxj1 is an f-box transcription factor expressed in ciliated cells and shown to be required for cilia formation by gene deletion in a mouse model. To identify a specific role for foxj1 in directing the ciliated cell phenotype, we evaluated the capacity of foxj1 to induce ciliogenesis and direct cilia assembly. In a primary culture model of wild-type mouse airway epithelial cells, foxj1 expression preceded the appearance of cilia and in cultured foxj1 null cells cilia did not develop. Delivery of foxj1 to polarized epithelial cell lines and primary cultured alveolar epithelial cells failed to promote ciliogenesis. Similarly, delivery of foxj1 to wild-type airway epithelial cells did not enhance the total number ofciliated cells. In contrast, delivery of foxj1 to null cells resulted in the appearance of cilia. Analysis revealed that, in the absence of foxj1, null cells contained cilia precursor basal bodies, indicating prior commitment to ciliogenesis. However, the basal bodies were disorganized within the apical compartment and failed to dock with the apical membrane. Reconstitution of foxj1 in null cells restored normal basal body organization, resulting in axoneme growth. Thus foxj1 functions in late-stage ciliogenesis to regulate programs promoting basal body docking and axoneme formation in cells previously committed to the ciliated cell phenotype.
机译：将未分化的气道上皮细胞定为纤毛细胞所需的因素尚不清楚。细胞超微结构分析表明，纤毛细胞的活性激活了一个多阶段程序，涉及纤毛前体蛋白的合成和大分子复合物的组装。 Foxj1是在纤毛细胞中表达的f-box转录因子，在小鼠模型中被证明是通过基因缺失形成纤毛所必需的。为了确定foxj1在指导纤毛细胞表型中的特定作用，我们评估了foxj1诱导纤毛发生和直接纤毛组装的能力。在野生型小鼠气道上皮细胞的原始培养模型中，foxj1表达先于纤毛出现，而在培养的foxj1中未发育纤毛。 foxj1传递到极化的上皮细胞系和原代培养的肺泡上皮细胞未能促进纤毛发生。同样，将foxj1递送至野生型气道上皮细胞并没有增加纤毛细胞的总数。相反，将foxj1递送至空细胞导致了纤毛的出现。分析表明，在不存在foxj1的情况下，空细胞中含有纤毛前体基体，表明其先后致力于纤毛发生。然而，基体在根尖腔内杂乱无章，无法与根尖膜对接。无效细胞中foxj1的重建恢复了正常的基础身体组织，导致轴突生长。因此，foxj1在晚期纤毛形成过程中起着调节程序的作用，该程序促进了先前致力于纤毛细胞表型的细胞中的基底体对接和轴突形成。

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