Age-dependent changes in the expression of matrix components in the mouse eye

Age-dependent changes in the expression of matrix components in the mouse eye
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DOI:
10.1006/exer.2000.0972
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发表时间:
2001-04-01
影响因子:
3.4
通讯作者:
Vuorio, E
Vuorio, E
中科院分区:
医学3区
文献类型:
--
作者:
Ihanamäki, T;Salminen, H;Vuorio, E

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虽然早期已经记录了眼内“软骨特异性”胶原蛋白的存在,但对它们在眼发育、生长和衰老过程中的合成速率知之甚少。本研究的目的是跟踪正常和转基因Del 1小鼠眼内细胞外基质关键成分的mRNA水平和分布的变化,在眼生长和衰老过程中,在IT型胶原基因中存在短缺失突变。通过北方分析研究从小鼠眼睛提取的总RNA的I、II、III型mRNA水平。VI、IX和XI胶原蛋白、双糖链蛋白聚糖、脂调蛋白和核心蛋白聚糖。本研究的一个主要发现是,随着年龄的增长,眼睛中I型和II型胶原蛋白的mRNA水平显著降低。III型和VI型胶原和蛋白多糖的mRNA水平的变化较小。通过免疫组化进行眼内II型和IM胶原的定位。尽管IT型胶原mRNA水平降低,但免疫组织化学证实了该蛋白在衰老小鼠眼中的广泛分布。表明它的周转缓慢尽管Del1突变导致眼睛逐渐变性病变,但蛋白质的分布基本保持不变。在小鼠眼睛中II型胶原蛋白的广泛分布和显着的下调,在老化可能解释逐渐发展的退行性病变,特别是在转基因的Del 1小鼠的眼睛,突变型TT型胶原蛋白链的生产也有助于该过程。(C)北京:科学出版社.
Although the presence of 'cartilage-specific' collagens in the eye has been documented earlier, very little is known about their synthesis rates during ocular development, growth and aging. The purpose of the present study was to follow changes in the mRNA levels and distribution of key components of the extracellular matrix in the eyes of normal and transgenic Del1 mice, harboring a short deletion mutation in the type IT collagen gene, during ocular growth and aging. Total RNAs extracted from mouse eyes were studied by Northern analysis for mRNA levels of type I, II, III. VI, IX and XI collagens, biglycan, libromodulin and decorin. A predominant finding of the present study was the marked reduction in the mRNA levels of type I and II collagens in the eye upon aging. The changes in the mRNA levels of type III and VI collagen and proteoglycans were smaller. Localization of type II and IM collagen in the eye was performed by immunohistochemistry. Despite the reduction in the type IT collagen mRNA levels, immunohistochemistry confirmed widespread distribution of the protein also in aging mouse eyes. suggesting its slow turnover. Although the Del1 mutation caused gradual degenerative lesions in the eyes, the distribution of the protein remained essentially unchanged. The widespread distribution and marked downregulation of type II collagen production in the mouse eye upon aging probably explain the gradual development of degenerative lesions, particularly in the eyes of transgenic Del1 mice, where production of mutant type TT collagen chains also contributes to the process. (C) 2001 Academic Press.