BMP4 promotes a phenotype change of an esophageal squamous epithelium via up-regulation of KLF4
BMP4 promotes a phenotype change of an esophageal squamous epithelium via up-regulation of KLF4
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BMP4 通过上调 KLF4 促进食管鳞状上皮的表型变化。
DOI：
10.1016/j.yexmp.2016.09.007
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发表时间：
2016-10-01
影响因子：
3.6
通讯作者：
Fang, Dianchun
中科院分区：
文献类型：
--
作者：
Yan, Wu;Zhang, Haoxiang;Fang, Dianchun
简介：Barrett食管是一种化生性病变。然而，所涉及的细胞和分子机制知之甚少。本研究旨在探讨KLF 4和BMP 4在Barrett上皮发病中的作用。材料与方法：采用免疫组化方法检测KLF 4、BMP 4、CDX 2、MUC 2和MUC 5AC在人食管标本中的表达。对人食管鳞状上皮细胞进行胆汁酸处理并用于转染实验。结果：在人组织中，Barrett's上皮中BMP 4、p-Smad 1/5/8和KLF 4的表达较强。此外，胆汁酸还可增加食管上皮细胞BMP 4、KLF 4、p-Smad 1/5/8、CDX 2、MUC 2和MUC 5ac的表达，并呈时间依赖性。BMP 4可上调KLF 4、CDX 2、MUC 2和MUC 5ac的表达，而BMP 4特异性拮抗剂Noggin可阻断BMP 4诱导的KLF 4、CDX 2、MUC 2和MUC 5ac的表达。结论：BMP 4通过上调KLF 4表达促进食管鳞状上皮细胞表型的改变，而Noggin不能阻断KLF 4表达载体转染的细胞中KLF 4、CDX 2、MUC 2和MUC 5ac的表达。(C)2016 Elsevier Inc. All rights reserved.
Introduction: Barrett's esophagus is a metaplastic lesion. However, the cellular and molecular mechanisms involved are poorly understood. The aim of this study was to investigate the roles of KLF4 and BMP4 in the pathogenesis of Barrett's epithelium.Materials and methods: Immunohistochemistry was used to analyse the expression of KLF4, BMP4, CDX2, MUC2 and MUC5AC in human esophageal specimens. Human esophageal squamous epithelial cells were subjected to bile acid treatment and used in transfection experiments. Quantitative real-time PCR and Western blot analysis were used to detect the expression of KLF4, BMP4, CDX2, MUC2 and MUC5ac.Results: In human tissues, Barrett's epithelium strongly expressed BMP4, p-Smad1/5/8 and KLF4. Furthermore, bile acids increased the expression of BMP4, KLF4, p-Smad1/5/8, CDX2, MUC2 and MUC5ac in esophageal epithelial cells in a time-dependent manner. Moreover, we found that BMP4 up-regulated the expression of KLF4, CDX2, MUC2 and MUC5ac, but Noggin, a specific BMP4 antagonist, can block the expression of KLF4, CDX2, MUC2 and MUC5ac induced by BMP4. However, BMP4 cannot induce the expression of CDX2, MUC2 and MUC5ac in cells with KLF4 siRNA, and Noggin cannot block the expression of KLF4, CDX2, MUC2 and MUC5ac in cells transfected with the KLF4 expression vector.Conclusion: Our results demonstrate that BMP4 promotes a phenotype change of an esophageal squamous epithelium via up-regulation of KLF4. (C) 2016 Elsevier Inc. All rights reserved.