Mesenchymal transition in kidney collecting duct epithelial cells
Mesenchymal transition in kidney collecting duct epithelial cells
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DOI：
10.1152/ajprenal.00326.2007
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发表时间：
2008-05-01
影响因子：
4.2
通讯作者：
Matsell, Douglas G.
中科院分区：
文献类型：
--
作者：
Ivanova, Larissa;Butt, Michael J.;Matsell, Douglas G.
由组织瘢痕和纤维化引起的进行性器官损伤是包括慢性肾脏疾病在内的许多人类疾病共有的一种模式。本研究的目的是证实收集管（CD）上皮细胞在体外可以发生间充质转化（EMT）的假设。CDs经历EMT的机制是复杂的，涉及早期和晚期细胞事件。早期事件包括胰岛素样生长因子（IGF）诱导的Akt和GSK-3 β的快速磷酸化，与E-cadherin- β -catenin膜共定位的早期破坏、E-cadherin易位到核内体、β -catenin易位到细胞核以及Snail表达的增加有关。另一方面，转化生长因子- β 1诱导Smad3的早期激活及其向细胞核的易位，Erk1/2的磷酸化，以及E-cadherin膜定位的早期破坏。这些事件的后期后果包括细胞表型转化为间充质形态，与之相关的波形蛋白和α -平滑肌肌动蛋白表达增加，以及细胞总e -钙粘蛋白表达减少，早在刺激后24小时就可检测到。
Progressive organ damage due to tissue scarring and fibrosis is a paradigm shared by numerous human diseases including chronic kidney disease. The purpose of this study was to confirm the hypothesis that collecting duct (CD) epithelial cells can undergo mesenchymal transition (EMT) in vitro. The mechanism by which CDs undergo EMT is complex and involves both early and late cellular events. Early events include rapid insulin-like growth factor (IGF)-induced Akt and GSK-3 beta phosphorylation, associated with early disruption of E-cadherin-beta-catenin membrane colocalization, with translocation of E-cadherin to endosomes, with translocation of beta-catenin to the nucleus, and with an increase in Snail expression. Transforming growth factor-beta 1, on the other hand, induced early activation of Smad3 and its translocation to the nucleus, Erk1/2 phosphorylation, and early disruption of membrane E-cadherin localization. The late consequences of these events included a phenotypic transformation of the cells to a mesenchymal morphology with associated increase in vimentin and alpha-smooth muscle actin protein expression and a decrease in total cellular E-cadherin expression, detectable as early as 24 h after stimulation.