TGFβ receptor expression in lens:: Implications for differentiation and cataractogenesis
TGFβ receptor expression in lens:: Implications for differentiation and cataractogenesis
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DOI：
10.1006/exer.2001.1001
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发表时间：
2001-06-01
影响因子：
3.4
通讯作者：
McAvoy, JW
中科院分区：
文献类型：
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作者：
De Iongh, RU;Gordon-Thomson, C;McAvoy, JW
TGF β诱导某些形式白内障的特征性变化。然而，透镜上皮细胞对TGF β的反应性是年龄依赖性的;断奶和成年，但不是新生儿，透镜上皮细胞响应。本研究探讨了大鼠透镜发育过程中TGF β受体（T β RI和T β RII）的表达以及FGF-2对TGF β反应性和T β R表达的影响。采用免疫荧光、免疫印迹、RT-PCR和原位杂交等方法检测T β R的时空表达模式。使用透镜外植体研究FGF-2对TGF β反应性和T β R表达的影响。在透镜上皮中，在P3时几乎没有或没有检测到免疫反应性，但在P21时，T β RI和T β RII有明显的反应性。两种受体的反应性也被发现在过渡区和皮质的分化纤维在两个年龄。透镜膜提取物的Western印迹法鉴定了多种分子量形式的T β RI（30、50、90 kDa）和T β RII（70-120 kDa）。原位杂交与大鼠探针Alk 5（T β RI）表明，透镜表达Alk 5 mRNA的上皮细胞和纤维在整个发展。大鼠T β RII探针显示，在整个发育过程中，透镜纤维和P21时的透镜上皮细胞中T β RII mRNA有不同的表达，但P3时没有。体外研究表明，来自P9大鼠的透镜上皮外植体对TGF β的反应没有发生白内障变化，但P13外植体发生白内障变化。向P9外植体中添加FGF-2诱导TPR免疫反应性增加，并增强透镜上皮细胞对TGF β的反应能力。这些数据表明，出生后发育期间（P3-P21）透镜上皮细胞中TGF β受体表达的总体增加是TGF β反应性的年龄相关变化的基础。结果还表明，透镜细胞可能表达多种形式的TPR。在整个透镜发育过程中，T β R在透镜纤维中的表达以及FGF诱导的T β R表达增强表明TGF β信号在FGF诱导的反应和纤维分化过程中的作用。(C)北京：科学出版社.
TGF beta induces changes characteristic of some forms of cataract. However, the responsiveness of lens epithelial cells to TGF beta is age-dependent; weanling and adult, but not neonatal, lens epithelial cells respond. This study investigated TGF beta receptor (T beta RI and T beta RII) expression during rat lens development and the effects of FGF-2 on TGF beta responsiveness and T betaR expression. Immunofluorescence, immunoblotting, RT-PCR and in situ hybridization were used to examine the spatio-temporal expression patterns of T betaR. Lens explants were used to investigate the effects of FGF-2 on TGF beta responsiveness and T betaR expression. In the lens epithelium, little or no immunoreactivity was detected at P3 but at P21 there was distinct reactivity for T beta RI and T beta RII. Reactivity for both receptors was also found in the differentiating fibers in the transitional zone and cortex at both ages. Western blotting of lens membrane extracts identified multiple molecular weight forms of T beta RI (30, 50, 90 kDa) and T beta RII (70-120 kDa). In situ hybridization with a rat probe for Alk5 (T beta RI) showed that the lens expresses Alk5 mRNA in epithelium and fibers throughout development. A rat T beta RII probe revealed distinct expression of a T beta RII mRNA in lens fibers throughout development and in the lens epithelium at P21 but not at P3. In vitro studies showed that lens epithelial explants from P9 rats did not undergo cataractous changes in response to TGF beta but P13 explants did. Addition of FGF-2 to P9 explants induced increased TPR immunoreactivity and enhanced the competency of lens epithelial cells to respond to TGF beta. These data indicate that the overall increased expression of TGF beta receptors in lens epithelium during postnatal development (P3-P21) underlies an age-related change in TGF beta responsiveness. The results also suggest that lens cells may express multiple forms of TPR. Expression of T betaR in lens fibers throughout lens development and the induction of enhanced T betaR expression by FGF suggest a role for TGF beta signaling during FGF-induced responses and fiber differentiation. (C) 2001 Academic Press.