大鼠晶状体形态发生过程中与层粘连蛋白结合的整合素及其在纤维分化过程中的调控

Laminin-binding integrins in rat lens morphogenesis and their regulation during fibre differentiation.

作者信息

Wederell Elizabeth D, Brown Heidi, O'connor Michael, Chamberlain Coral G, McAvoy John W, de Iongh Robbert U

机构信息

Save Sight Institute and Department of Clinical Ophthalmology and Eye Health, The University of Sydney, NSW 2006, Australia; Department of Anatomy and Histology and Institute for Biomedical Research (F13), The University of Sydney, NSW 2006, Australia.

出版信息

Exp Eye Res. 2005 Sep;81(3):326-39. doi: 10.1016/j.exer.2005.02.005.

DOI:10.1016/j.exer.2005.02.005

PMID:16129100

Abstract

Mammalian lens development involves cell-cell and cell-ECM interactions. As integrins are a major family of cell adhesion molecules, we examined the expression patterns of several integrin subunits (alpha3A, alpha3B, alpha6A, alpha6B, beta1 and beta4) during rat lens development. RT-PCR, in situ hybridisation, immunofluorescence and immunoblotting were used to investigate expression of integrin subunits during lens development and differentiation. RT-PCR showed expression of alpha3A, alpha6A, alpha6B and beta1A but not alpha3B or beta4 subunits in postnatal rat lenses. Each subunit displayed distinct spatio-temporal expression patterns. beta1 integrin was expressed in both epithelium and fibres. alpha3A subunit expression was restricted to the epithelium; expression ceased abruptly at the lens equator. Expression of the alpha6A subunit increased during fibre differentiation, whereas alpha6B expression was predominantly associated with epithelial cells during lens development. In lens epithelial explants, FGF induced some of the changes in integrin expression that are characteristic of fibre differentiation in vivo. One notable exception was the inability of FGF to reproduce the distinctive down-regulation of the alpha3 isoform that is associated with initiation of elongation in vivo. Interestingly, vitreous treatment was able to reproduce this shift in alpha3 expression indicating that another factor(s), in addition to FGF, may be required for full and complete transition from an epithelial cell to a fibre cell. Integrin subunit expression therefore appears to be highly regulated during lens development and fibre differentiation with evidence of major changes in alpha3 and alpha6 isoform expression. These results indicate that integrins may play important roles in development and growth of the lens. How specific integrin subunits influence the behaviour of cells in different developmental compartments of the lens remains to be determined.

摘要

哺乳动物晶状体的发育涉及细胞间和细胞与细胞外基质（ECM）的相互作用。由于整合素是细胞黏附分子的主要家族，我们研究了几种整合素亚基（α3A、α3B、α6A、α6B、β1和β4）在大鼠晶状体发育过程中的表达模式。采用逆转录聚合酶链反应（RT-PCR）、原位杂交、免疫荧光和免疫印迹技术来研究整合素亚基在晶状体发育和分化过程中的表达。RT-PCR结果显示，出生后大鼠晶状体中存在α3A、α6A、α6B和β1A亚基的表达，但不存在α3B或β4亚基的表达。每个亚基都呈现出独特的时空表达模式。β1整合素在上皮细胞和纤维细胞中均有表达。α3A亚基的表达局限于上皮细胞；在晶状体赤道处表达突然停止。α6A亚基的表达在纤维分化过程中增加，而α6B的表达在晶状体发育过程中主要与上皮细胞相关。在晶状体上皮外植体中，成纤维细胞生长因子（FGF）诱导了一些整合素表达的变化，这些变化是体内纤维分化的特征。一个显著的例外是，FGF无法重现与体内伸长起始相关的α3异构体独特的下调。有趣的是，玻璃体处理能够重现α3表达的这种转变，这表明除了FGF之外，可能还需要其他因子才能完全从上皮细胞转变为纤维细胞。因此，在晶状体发育和纤维分化过程中，整合素亚基的表达似乎受到高度调控，α3和α6异构体表达有重大变化的证据。这些结果表明，整合素可能在晶状体的发育和生长中发挥重要作用。特定的整合素亚基如何影响晶状体不同发育区室中细胞的行为仍有待确定。