Excess Transforming Growth Factor-α Changed the Cell Properties of Corneal Epithelium and Stroma.
Excess Transforming Growth Factor-α Changed the Cell Properties of Corneal Epithelium and Stroma.
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过量的转化生长因子-α 改变了角膜上皮和基质的细胞特性。
DOI：
10.1167/iovs.61.8.20
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发表时间：
2020
影响因子：
4.4
通讯作者：
Zhang,Yujin
中科院分区：
文献类型：
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作者：
Zhang,Lingling;Yuan,Yong;Yeh,Lung-Kun;Dong,Fei;Zhang,Jianhua;Okada,Yuka;Kao,WinstonWY;Liu,Chia-Yang;Zhang,Yujin
目的：探讨小鼠发育过程中过度表达转化生长因子-α(转化生长因子-α)所致的角膜异常。方法：用多西环素从胚胎第0天或出生后第0天开始，诱导Kera RT/Tf-α小鼠在胚胎第0天或出生后0天至不同发育阶段过表达转化生长因子-α。将经多西环素诱导的双基因小鼠定义为转化生长因子αECK小鼠(角膜基质细胞过度表达转化生长因子α)。用苏木精-伊红染色、免疫荧光染色和透射电子显微镜观察小鼠眼部组织学改变。结果：在转化生长因子αECK小鼠中，转化生长因子α过表达导致角膜混浊。随着小鼠的发育，过量的转化生长因子-α最初导致角膜上皮细胞的增生和随后的上皮变性，伴随而来的是角膜上皮细胞周边K12的表达逐渐减少，K13向角膜中心的表达增加。有趣的是，K14在转化生长因子-αECK小鼠的角膜上皮各层均有表达，而对照组仅在基底层表达。透射电子显微镜下可见转化生长因子-α小鼠角膜上皮细胞间桥粒丢失。在转化生长因子αECK小鼠中，角化蛋白聚糖的表达被取消，α-SMA的表达增加，而COL1a1、COL1a2和COL5a1的表达降低。结论：过量的转化生长因子-α-α对小鼠发育过程中的角膜形态发生有不利影响，其机制可能是改变了角膜上皮细胞的命运，使角膜上皮细胞呈现结膜表型表达，角质形成细胞向肌成纤维细胞表型转化。
Purpose: This study is to investigate the corneal anomaly caused by excess transforming growth factor-α (TGF-α) during mouse development.Methods: Bitransgenic Kera RT/TGF-α mice, generated via cross-mating tetO-TGF-α and Kera RT mice, were induced to overexpress TGF-α by doxycycline commencing at embryonic day 0 or postnatal day 0 to different developmental stages. Bitransgenic mice with doxycycline induction were defined as TGF-α ECK mice (TGF-α excess expression by corneal keratocytes). Mouse eyes were examined by hematoxylin and eosin staining, immunofluorescent staining and transmission electron microscopy. Protein and RNA from mouse cornea were subjected to western blotting and real-time quantitative polymerase chain reaction.Results: In TGF-α ECK mice, TGF-α overexpression resulted in corneal opacity. Excess TGF-α initially caused corneal epithelial hyperplasia and subsequent epithelium degeneration as the mouse developed, which was accompanied by gradually diminished K12 expression from the periphery of corneal epithelium and increased K13 expression toward the corneal center. Interestingly, K14 was detected in all layers of corneal epithelium of TGF-α ECK mice, whereas it was limited at basal layer of controls. Transmission electron microscopy showed desmosome loss between corneal epithelial cells of TGF-α ECK mice. In TGF-α ECK mice, keratocan expression was abolished; α-SMA expression was increased while expression of Col1a1, Col1a2, and Col5a1 was diminished. Cell proliferation increased in the corneal epithelium and stroma, but not in the endothelium of TGF-α ECK mice.Conclusions: Excess TGF-α had detrimental effects on corneal morphogenesis during mouse development in that it changed the cell fate of corneal epithelial cells to assume conjunctival phenotypic expression of K13, and keratocytes to myofibroblast phenotype.