IMMIGRATION EXCLUSION
IMMIGRATION EXCLUSION
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DOI：
10.1002/9780470514771.ch5
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发表时间：
2007-01-01
期刊：
影响因子：
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通讯作者：
Davidann, Jon Thares
中科院分区：
文献类型：
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作者：
Davidann, Jon Thares
弹性蛋白在妊娠晚期由于其mRNA浓度的增加而迅速沉积在弹性组织如动脉、肺和皮肤中。病理状态可由先天性弹性蛋白不足或紊乱（皮肤拉克萨）引起。其他弹性蛋白缺陷可能是由于过度的弹性蛋白溶解或基因剂量效应。在前者中，高周转率可以通过测量尿液中的弹性蛋白降解产物来评估。皮肤成纤维细胞的过度弹性蛋白积累是遗传性疾病的特征，如Buschke-Ollenendorff综合征、哈钦森-吉尔福德早衰症和瘢痕疙瘩。弹性蛋白的表达受肽生长因子、类固醇激素和佛波醇酯的调节，其中转化生长因子β（TGF-β）是一种特别有效的上调因子，主要通过稳定mRNA发挥作用。最近的证据表明，皮肤拉克萨成纤维细胞表达很少或没有弹性蛋白具有正常的转录活性，但弹性蛋白mRNA降解率异常。TGF-β通过mRNA稳定化基本上逆转了这种缺陷。目前的研究探讨了弹性蛋白mRNA的3′非翻译区存在稳定性决定簇的假说。弹性蛋白表达的转录后控制似乎是一种主要的调控机制。
Elastin is rapidly deposited during late gestation in resilient tissues such as the arteries, lungs and skin owing to increased concentration of its mRNA. Pathological states can arise from congenital insufficiency or disorganization of elastin (cutis laxa). Other elastin deficiencies may be due to excess elastolysis or gene dosage effects. In the former, high turnover rates can be assessed by measurements of elastin degradation products in urine. Excess elastin accumulation by skin fibroblasts is characteristic of genetic diseases such as Buschke–Ollendorff syndrome, Hutchinson‐Gilford progeria and keloid. Elastin expression is modulated by peptide growth factors, steroid hormones and phorbol esters, among which transforming growth factor β (TGF‐β) is an especially potent up‐regulator, acting largely through stabilization of mRNA. Recent evidence indicates cutis laxa fibroblasts that express little or no elastin have normal transcriptional activity but abnormal rates of elastin mRNA degradation. This defect is substantially reversed by TGF‐β through mRNA stabilization. Current studies explore the hypothesis that stability determinants lie within the 3′ untranslated region of elastin mRNA. Post‐transcriptional control of elastin expression appears to be a major regulatory mechanism.