Abstract

MUC4 is a predominant membrane-tethered mucin lubricating and protecting the epithelial surface and playing various biological roles in the renewal and differentiation of epithelial cells, cell signaling, cell adhesion, and carcinogenesis. Interestingly, recent studies have demonstrated that MUC4 expression regulates the epithelial-mesenchymal transition (EMT) of cancer cells in ovarian, pancreatic, and lung cancer. However, the effects of MUC4 expression on EMT in human airway epithelial cells are not yet well known. Here, we describe the effects of transforming growth factor beta 1 (TGF-β1)-induced MUC4 expression on EMT and evaluate its downstream signaling pathway in human airway epithelial cells. In human airway epithelial NCI-H292 cells, exposure to TGF-β1 induced expression of MUC4, CDH2, VIM and SNAI1 genes and encoded by them proteins, MUC4, N-cadherin, vimentin and Snail, and reduced the level of CDH1 and its product, E-cadherin. In MUC4-knockdown cells, TGF-β1-induced expression levels of MUC4, CDH2, VIM and SNAI1 and corresponding proteins were suppressed, but CDH1 and E-cadherin levels were not. In addition, TGF-β1-induced phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) was suppressed, but that of Smad2/3, Akt, and p38 was not. The results of this study suggest that MUC4 silencing inhibits TGF-β1-induced EMT via the ERK1/2 pathway, and a possible role of MUC4 in the induction of EMT in human airway epithelial cells.

中文翻译：

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MUC4 沉默通过人气道上皮 NCI-H292 细胞中的 ERK1/2 通路抑制 TGF-β1 诱导的上皮-间质转化

摘要

MUC4 是一种主要的膜系留粘蛋白，可润滑和保护上皮表面，并在上皮细胞的更新和分化、细胞信号传导、细胞粘附和致癌作用中发挥各种生物学作用。有趣的是，最近的研究表明 MUC4 表达调节卵巢癌、胰腺癌和肺癌中癌细胞的上皮间质转化 (EMT)。然而，MUC4表达对人气道上皮细胞 EMT的影响尚不清楚。在这里，我们描述了转化生长因子 β1（TGF-β1）诱导的MUC4表达对 EMT 的影响，并评估了其在人气道上皮细胞中的下游信号通路。在人气道上皮 NCI-H292 细胞中，暴露于 TGF-β1 诱导表达MUC4、CDH2、VIM和SNAI1基因以及由它们编码的蛋白质 MUC4、N-钙粘蛋白、波形蛋白和 Snail，降低了CDH1及其产物 E-钙粘蛋白的水平。在MUC4敲低细胞中，TGF-β1 诱导的MUC4、CDH2、VIM和SNAI1以及相应蛋白质的表达水平受到抑制，但CDH1和 E-钙粘蛋白水平没有受到抑制。此外，TGF-β1 诱导的细胞外信号调节激酶 1/2 (ERK1/2) 的磷酸化受到抑制，但 Smad2/3、Akt 和 p38 的磷酸化不受抑制。本研究结果表明MUC4沉默通过ERK1/2 通路抑制 TGF-β1 诱导的 EMT ，以及 MUC4 在诱导人气道上皮细胞 EMT 中的可能作用。