ERK5 positively regulates cigarette smoke-induced urocystic epithelial-mesenchymal transition in SV-40 immortalized human urothelial cells
ERK5 positively regulates cigarette smoke-induced urocystic epithelial-mesenchymal transition in SV-40 immortalized human urothelial cells
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DOI：
10.3892/or.2015.4130
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发表时间：
2015-09-01
期刊：
影响因子：
4.2
通讯作者：
Zhong, Caiyun
中科院分区：
文献类型：
--
作者：
Geng, Hao;Zhao, Li;Zhong, Caiyun
膀胱癌被普遍认为是一个重大的公共卫生问题。大量证据表明，香烟烟雾（CS）是膀胱癌的主要危险因素。然而，CS诱发膀胱癌的机制尚未完全阐明。 CS诱导的上皮间质转化（EMT）在细胞恶性转化中发挥着重要作用。 ERK5（MAPK 家族中研究较少的成员）在调节 CS 触发的 EMT 中的作用尚未得到研究。本研究的目的是探讨 ERK5 在 CS 诱导的尿囊细胞 EMT 中的调节作用。 SV-40永生化正常人尿路上皮细胞（SV-HUC-1）用作体外CS暴露模型。通过细胞形态、侵袭能力以及上皮和间质标志物表达的变化来评估 EMT 表型改变。通过蛋白质印迹和定量逆转录聚合酶链反应 (qRT-PCR) 分析蛋白质和 mRNA 表达水平。使用特定抑制剂进行 ERK5 抑制研究。 SV-HUC-1 细胞暴露于 CS 会诱导形态变化，增强侵袭能力，减少上皮标志物表达并增加间充质标志物表达。重要的是，我们首次证明 ERK5 正向调节尿路上皮细胞中 CS 介导的 EMT，CS 促进 ERK5 激活，并且 ERK5 抑制可逆转 CS 触发的 EMT 表型改变。
Bladder cancer is universally acknowledged as a significant public health issue. Abundant evidence shows that cigarette smoke (CS) is the primary risk factor for bladder cancer. However, the mechanism of CS-induced bladder cancer has not been fully elucidated. CS-induced epithelial-mesenchymal transition (EMT) is critically involved in cell malignant transformation. The role of ERK5, the lesser studied member of the MAPK family, in regulating CS-triggered EMT has not yet been investigated. The objective of the present study was to investigate the regulatory role of ERK5 in CS-induced urocystic EMT. SV-40 immortalized normal human urothelial cells (SV-HUC-1) were used as in vitro CS exposure models. EMT phenotypic alterations were assessed by changes in cell morphology, invasive capacity, as well as expression of epithelial and mesenchymal markers. Protein and mRNA expression levels were analyzed by western blotting and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). ERK5 inhibition studies were performed with a specific inhibitor. Exposure of SV-HUC-1 cells to CS induced morphological change, enhanced invasive capacity, reduced epithelial marker expression and increased mesenchymal marker expression. Importantly, we demonstrated for the first time that ERK5 positively regulated CS-mediated EMT in urothelial cells, as evidenced by the findings that CS promoted ERK5 activation, and that the CS-triggered alteration in the EMT phenotype was reversed by ERK5 inhibition.