Mahmood R, Flanders K C, Morriss-Kay G M
Laboratory of Chemoprevention, National Institutes of Health, Bethesda, MD 20892, USA.
Anat Embryol (Berl). 1995 Jul;192(1):21-33. doi: 10.1007/BF00186988.
In a previous study we investigated the effects of RA excess on TGF beta protein localization in early postimplantation stages of mouse development. Here we extend this investigation by comparing the effects of retinoid deficiency with those of excess, and by comparing the effects of altered retinoid status on TGF beta protein and RNA transcript distribution. In vitamin A-deficient embryos, TGF beta 1 RNA and protein distribution were both unaltered compared with controls; conversely, TGF beta 2 protein levels were reduced while RNA levels remained normal. In RA-treated embryos, the previous study showed that intracellular TGF beta 1 levels were decreased, while those of extracellular TFG beta 1 were initially decreased but subsequently increased; here we found that TGF beta 1 RNA transcript levels were reduced following exposure to RA excess. TGF beta 2 showed a clear disparity between the effects of RA excess on protein and RNA transcript levels: RNA transcript distribution was unchanged or showed a slight increase in RA-treated embryos, whereas the previous results showed greatly reduced protein levels. The new results provide further evidence for interaction between retinoids and TGF beta s during mouse development, and indicate that retinoids are capable of differentially regulating TGF beta isoforms through mechanisms involving different stages in the process of TGF beta synthesis and secretion. The long-term nature of the effects of transient exposure to RA excess suggests that the mechanisms of RA-TGF beta interaction may be indirect.
在之前的一项研究中，我们调查了视黄酸过量对小鼠发育植入后早期阶段转化生长因子β（TGFβ）蛋白定位的影响。在此，我们通过比较维甲酸缺乏与过量的影响，以及比较维甲酸状态改变对TGFβ蛋白和RNA转录本分布的影响来扩展这项研究。在维生素A缺乏的胚胎中，与对照组相比，TGFβ1 RNA和蛋白分布均未改变；相反，TGFβ2蛋白水平降低，而RNA水平保持正常。在视黄酸处理的胚胎中，之前的研究表明细胞内TGFβ1水平降低，而细胞外TGFβ1水平最初降低但随后升高；在此我们发现，暴露于过量视黄酸后TGFβ1 RNA转录本水平降低。TGFβ2在视黄酸过量对蛋白和RNA转录本水平的影响之间表现出明显差异：RNA转录本分布未改变或在视黄酸处理的胚胎中略有增加，而之前的结果显示蛋白水平大幅降低。这些新结果为小鼠发育过程中维甲酸与TGFβ之间的相互作用提供了进一步证据，并表明维甲酸能够通过涉及TGFβ合成和分泌过程中不同阶段的机制差异性地调节TGFβ亚型。短暂暴露于过量视黄酸的影响具有长期性，这表明视黄酸 - TGFβ相互作用的机制可能是间接的。
