Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Am J Physiol Cell Physiol. 2022 Sep 1;323(3):C666-C677. doi: 10.1152/ajpcell.00228.2022. Epub 2022 Jul 11.
Elastin provides recoil to tissues that stretch such as the lung, blood vessels, and skin. It is deposited in a brief window starting in the prenatal period and extending to adolescence in vertebrates, and then slowly turns over. Elastin insufficiency is seen in conditions such as Williams-Beuren syndrome and elastin-related supravalvar aortic stenosis, which are associated with a range of vascular and connective tissue manifestations. Regulation of the elastin () gene occurs at multiple levels including promoter activation/inhibition, mRNA stability, interaction with microRNAs, and alternative splicing. However, these mechanisms are incompletely understood. Better understanding of the processes controlling gene expression may improve medicine's ability to intervene in these rare conditions, as well as to replace age-associated losses by re-initiating elastin production. This review describes what is known about the gene promoter structure, transcriptional regulation by cytokines and transcription factors, and posttranscriptional regulation via mRNA stability and micro-RNA and highlights new approaches that may influence regenerative medicine.
弹性蛋白为拉伸组织(如肺、血管和皮肤)提供弹性回复力。在脊椎动物中,它从胚胎期开始沉积在一个短暂的窗口内,并延伸到青春期,然后缓慢更新。弹性蛋白不足可见于威廉姆斯-贝伦综合征和弹性蛋白相关的主动脉瓣上狭窄等疾病,这些疾病与多种血管和结缔组织表现有关。弹性蛋白基因的调控发生在多个水平,包括启动子激活/抑制、mRNA 稳定性、与 microRNA 的相互作用以及选择性剪接。然而,这些机制尚未完全了解。更好地了解控制基因表达的过程可能会提高医学干预这些罕见疾病的能力,以及通过重新启动弹性蛋白的产生来替代与年龄相关的损失。这篇综述描述了已知的基因启动子结构、细胞因子和转录因子的转录调控,以及通过 mRNA 稳定性和 microRNA 的转录后调控,并强调了可能影响再生医学的新方法。