Peten E P, Striker L J, Garcia-Perez A, Striker G E
Renal Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Kidney Int Suppl. 1993 Jan;39:S55-8.
We have shown that the glomerulosclerotic lesions of mice transgenic for bovine growth hormone (bGH mice) consisted of a change in the phenotype of glomerular collagens and an elevation of the mRNAs for these collagens in whole kidney. The purpose of this study was to determine whether these phenotypic and quantitative changes were present in the glomeruli. We used the increased sensitivity afforded by reverse transcription followed by the polymerase chain reaction (RT-PCR) to detect type I collagen mRNA and a quantitative PCR assay to quantitate type IV collagen mRNA in microdissected glomeruli. There was a six- to eightfold increase in alpha 1IV collagen mRNA in the glomeruli of bGh mice. alpha 1(I) collagen mRNA was present in glomeruli of bGH mice, which is consistent with our previous findings that the sclerotic mesangium contained type I collagen peptides by immunofluorescence microscopy. Normal glomeruli did not contain detectable amounts of alpha 1I collagen mRNA. In summary, we found a phenotypic change in glomeruli of mice transgenic for bGH consisting of increased type IV collagen mRNA levels and the appearance of type I collagen mRNA. Thus, the development of glomerulosclerosis appeared to be at least partially regulated at a pretranslational level.
我们已经表明,转基因牛生长激素小鼠(bGH小鼠)的肾小球硬化病变包括肾小球胶原蛋白表型的改变以及全肾中这些胶原蛋白mRNA水平的升高。本研究的目的是确定这些表型和定量变化是否存在于肾小球中。我们利用逆转录后聚合酶链反应(RT-PCR)提供的更高灵敏度来检测I型胶原蛋白mRNA,并采用定量PCR分析法来定量微切割肾小球中的IV型胶原蛋白mRNA。bGh小鼠肾小球中的α1IV胶原蛋白mRNA增加了6至8倍。α1(I)胶原蛋白mRNA存在于bGH小鼠的肾小球中,这与我们之前的研究结果一致,即通过免疫荧光显微镜观察,硬化的系膜含有I型胶原蛋白肽。正常肾小球中未检测到α1I胶原蛋白mRNA。总之,我们发现转基因bGH小鼠的肾小球存在表型变化,包括IV型胶原蛋白mRNA水平升高和I型胶原蛋白mRNA的出现。因此,肾小球硬化的发展似乎至少部分在翻译前水平受到调控。