Requirement of podocalyxin in TGF-beta induced epithelial mesenchymal transition.

Requirement of podocalyxin in TGF-beta induced epithelial mesenchymal transition.
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DOI:
10.1371/journal.pone.0018715
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发表时间:
2011-04-12
期刊:
影响因子:
3.7
通讯作者:
Wilkins JA
Wilkins JA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Meng X;Ezzati P;Wilkins JA

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上皮间充质转化(EMT)的特征在于间充质特性的发展,如成纤维细胞样形态,细胞骨架结构改变和迁移潜力增强。我们报道了在TGF-β诱导的EMT过程中,CD 34家族成员podocalyxin(PODXL)的表达显著增加。PODXL在迁移的A549细胞的前缘富集。足糖萼蛋白表达的沉默减少了细胞皱褶的形成、扩散、迁移,并影响了在EMT期间通常变化的几种蛋白质的表达模式(例如,波形蛋白、E-钙粘蛋白)。EMT中的细胞骨架组装也被发现依赖于podocalyin的产生。含有足糖萼蛋白的免疫沉淀物的组成分析显示,1型胶原蛋白与这些分离株一致。还发现1型胶原蛋白与足糖萼蛋白在迁移细胞的前缘上共定位。与胶原蛋白的相互作用可能是足糖萼蛋白功能的一个重要方面。足糖萼蛋白是EMT样过程的重要调节因子,因为它调节上皮特征的丧失和运动表型的获得。
Epithelial mesenchymal transition (EMT) is characterized by the development of mesenchymal properties such as a fibroblast-like morphology with altered cytoskeletal organization and enhanced migratory potential. We report that the expression of podocalyxin (PODXL), a member of the CD34 family, is markedly increased during TGF-β induced EMT. PODXL is enriched on the leading edges of migrating A549 cells. Silencing of podocalyxin expression reduced cell ruffle formation, spreading, migration and affected the expression patterns of several proteins that normally change during EMT (e.g., vimentin, E-cadherin). Cytoskeletion assembly in EMT was also found to be dependent on the production of podocalyin. Compositional analysis of podocalyxin containing immunoprecipitates revealed that collagen type 1 was consistently associated with these isolates. Collagen type 1 was also found to co-localize with podocalyxin on the leading edges of migrating cells. The interactions with collagen may be a critical aspect of podocalyxin function. Podocalyxin is an important regulator of the EMT like process as it regulates the loss of epithelial features and the acquisition of a motile phenotype.
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