骨形态发生蛋白4（BMP4）通过上调KLF4促进食管鳞状上皮的表型改变。
BMP4 promotes a phenotype change of an esophageal squamous epithelium via up-regulation of KLF4.
作者信息
Yan Wu, Zhang Haoxiang, Li Jingwen, Shen Caifei, Xia Yiju, Wang Pu, Zhang Yafei, Feng Ji, Shao Shunzi, Yu Xiaona, Fang Dianchun
机构信息
Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
出版信息
Exp Mol Pathol. 2016 Oct;101(2):259-266. doi: 10.1016/j.yexmp.2016.09.007. Epub 2016 Sep 28.
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.
引言
巴雷特食管是一种化生病变。然而，其涉及的细胞和分子机制尚不清楚。本研究旨在探讨KLF4和BMP4在巴雷特上皮发病机制中的作用。
材料与方法
采用免疫组织化学分析人食管标本中KLF4、BMP4、CDX2、MUC2和MUC5AC的表达。人食管鳞状上皮细胞经胆汁酸处理后用于转染实验。采用定量实时PCR和蛋白质印迹分析检测KLF4、BMP4、CDX2、MUC2和MUC5ac的表达。
结果
在人体组织中，巴雷特上皮强烈表达BMP4、p-Smad1/5/8和KLF4。此外，胆汁酸以时间依赖性方式增加食管上皮细胞中BMP4、KLF4、p-Smad1/5/8、CDX2、MUC2和MUC5ac的表达。此外，我们发现BMP4上调KLF4、CDX2、MUC2和MUC5ac的表达，但BMP4特异性拮抗剂Noggin可阻断BMP4诱导的KLF4、CDX2、MUC2和MUC5ac的表达。然而，BMP4不能诱导KLF4小干扰RNA细胞中CDX2、MUC2和MUC5ac的表达，Noggin也不能阻断转染KLF4表达载体的细胞中KLF4、CDX2、MUC2和MUC5ac的表达。
结论
我们的结果表明，BMP4通过上调KLF4促进食管鳞状上皮的表型改变。
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