Anterior segment dysgenesis correlation with epithelial-mesenchymal transition in Smad4 knockout mice
Anterior segment dysgenesis correlation with epithelial-mesenchymal transition in Smad4 knockout mice
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Smad4 敲除小鼠眼前节发育不全与上皮间质转化的相关性
DOI：
10.18240/ijo.2016.07.02
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发表时间：
2016-07-18
影响因子：
1.4
通讯作者：
Zhang, Jin-Song
中科院分区：
文献类型：
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作者：
Li, Jing;Qin, Yu;Zhang, Jin-Song
目的：探讨Smad4缺陷小鼠晶状体发育的分子机制及彼得斯异常的发病机制。方法：采用Le -Cre转基因小鼠系选择性灭活外胚层表面的Smad4。采用病理学方法观察Smad4缺损眼前段的形态学变化。采用免疫组化染色法观察胚胎(E)第16.5天Smad4缺陷小鼠和对照小鼠前段E-cadherin、N-cadherin和α - sma的表达。采用实时定量聚合酶链反应（qPCR）检测Smad4缺陷小鼠和对照小鼠在E16.5时晶状体中Snail、Zeb1、Zeb2和Twist2的表达情况。结果：眼表外胚层Smad4的条件缺失导致角膜发育不良、虹膜角膜角闭合、角膜小颗粒粘连和类似彼得斯的白内障异常。Smad4功能缺失可抑制Smad4缺陷眼晶状体上皮细胞和角膜上皮细胞中E-cadherin的表达。N -钙粘蛋白在角膜上皮和角膜基质中的表达上调。突变眼未来小梁网区E-cadherin和N-cadherin均下调。qPCR结果显示，突变体中Twist2的表达量显著增加(P
AIM: To explore the molecular mechanisms in lens development and the pathogenesis of Peters anomaly in Smad4 defective mice.METHODS: Le -Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively. Pathological techniques were used to reveal the morphological changes of the anterior segment in Smad4 defective eye. Immunohistochemical staining was employed to observe the expression of E-cadherin, N-cadherin and alpha-SMA in anterior segment of Smad4 defective mice and control mice at embryonic (E) day 16.5. Real-time quantitative polymerase chain reaction (qPCR) was performed to detect the expression of Snail, Zeb1, Zeb2 and Twist2 in lens of Smad4 defective mice and control mice at E16.5.RESULTS: Conditional deletion of Smad4 on eye surface ectoderm resulted in corneal dysplasia, iridocorneal angle closure, corneolenticular adhesions and cataract resembling Peters anomaly. Loss of Smad4 function inhibited E-cadherin expression in the lens epithelium cells and corneal epithelium cells in Smad4 defective eye. Expression of N -cadherin was up -regulated in corneal epithelium and corneal stroma. Both E-cadherin and N-cadherin were down-regulated at the future trabecular meshwork region in mutant eye. The qPCR results showed that the expression of Twist2 was increased significantly in the mutant lens (P