Delineation of the Key Aspects in the Regulation of Epithelial Monolayer Formation
Delineation of the Key Aspects in the Regulation of Epithelial Monolayer Formation
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DOI：
10.1128/mcb.01435-12
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发表时间：
2013-07-01
影响因子：
5.3
通讯作者：
Jennings, Paul
中科院分区：
文献类型：
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作者：
Aschauer, Lydia;Gruber, Leonhard N.;Jennings, Paul
上皮屏障的形成、维持和修复对全身动态平衡至关重要。然而，参与上皮组织成熟的分子事件还没有完全确定。为此，我们利用转录、代谢和功能参数研究了参与肾上皮近端小管单层成熟的分子过程。我们揭示了成熟过程中转录调节、能量代谢和营养利用的深刻动态变化。增殖的细胞表现出高的糖酵解率和脂肪酸合成基因(FASN)的高转录水平，而成熟的细胞表现出低的糖酵解率，增强的氧化能力，并优先表达β氧化基因。几种黏附蛋白(CDH1、-4、-16)和紧密连接蛋白(TJP3、CLDN2、-10)的表达和定位发生了动态变化。参与近曲小管分化功能、纤毛生物发生(BBS1)和运输(ATP1A1和ATP1B1)的基因在上皮成熟过程中表达增加。利用TransAm转录因子活性检测，我们可以证明P53和FOXO1在成熟细胞中高度活跃，而HIF1a和c-myc在增殖细胞中高度活跃。这里提出的数据将是非常宝贵的进一步描绘复杂的动态细胞过程中涉及的上皮细胞调节。
The formation, maintenance, and repair of epithelial barriers are of critical importance for whole-body homeostasis. However, the molecular events involved in epithelial tissue maturation are not fully established. To this end, we investigated the molecular processes involved in renal epithelial proximal-tubule monolayer maturation utilizing transcriptomic, metabolomic, and functional parameters. We uncovered profound dynamic alterations in transcriptional regulation, energy metabolism, and nutrient utilization over the maturation process. Proliferating cells exhibited high glycolytic rates and high transcript levels for fatty acid synthesis genes (FASN), whereas matured cells had low glycolytic rates, increased oxidative capacity, and preferentially expressed genes for beta oxidation. There were dynamic alterations in the expression and localization of several adherens (CDH1, -4, and -16) and tight junction (TJP3 and CLDN2 and -10) proteins. Genes involved in differentiated proximal-tubule function, cilium biogenesis (BBS1), and transport (ATP1A1 and ATP1B1) exhibited increased expression during epithelial maturation. Using TransAM transcription factor activity assays, we could demonstrate that p53 and FOXO1 were highly active in matured cells, whereas HIF1A and c-MYC were highly active in proliferating cells. The data presented here will be invaluable in the further delineation of the complex dynamic cellular processes involved in epithelial cell regulation.