UCD Clinical Research Centre, School of Medicine, University College Dublin, Ireland.
UCD Clinical Research Centre, School of Medicine, University College Dublin, Ireland.
Exp Eye Res. 2020 Apr;193:107975. doi: 10.1016/j.exer.2020.107975. Epub 2020 Feb 15.
Lysyl Oxidase Like 1 (LOXL1) is a gene that encodes for the LOXL1 enzyme. This enzyme is required for elastin biogenesis and collagen cross-linking, polymerising tropoelastin monomers into elastin polymers. Its main role is in elastin homeostasis and matrix remodelling during injury, fibrosis and cancer development. Because of its vast range of biological functions, abnormalities in LOXL1 underlie many disease processes. Decreased LOXL1 expression is observed in disorders of elastin such as Cutis Laxa and increased expression is reported in fibrotic disease such as Idiopathic Pulmonary Fibrosis. LOXL1 is also downregulated in the lamina cribrosa in pseudoexfoliation glaucoma and genetic variants in the LOXL1 gene have been linked with an increased risk of developing pseudoexfoliation glaucoma and pseudoexfoliation syndrome. However the two major risk alleles are reversed in certain ethnic groups and are present in a large proportion of the normal population, implying complex genetic and environmental regulation is involved in disease pathogenesis. It also appears that the non-coding variants in intron 1 of LOXL1 may be involved in the regulation of LOXL1 expression. Gene alteration may occur via a number of epigenetic and post translational mechanisms such as DNA methylation, long non-coding RNAs and microRNAs. These may represent future therapeutic targets for disease. Environmental factors such as hypoxia, oxidative stress and ultraviolet radiation exposure alter LOXL1 expression, and it is likely a combination of these genetic and environmental factors that influence disease development and progression. In this review, we discuss LOXL1 properties, biological roles and regulation in detail with a focus on pseudoexfoliation syndrome and glaucoma.
赖氨酰氧化酶样蛋白 1（LOXL1）是一种编码 LOXL1 酶的基因。这种酶对于弹性蛋白的生物合成和胶原交联是必需的，它将原弹性蛋白单体聚合形成弹性蛋白聚合物。它的主要作用是在损伤、纤维化和癌症发展过程中维持弹性蛋白的内稳态和基质重塑。由于其广泛的生物学功能，LOXL1 的异常与许多疾病过程有关。在弹性蛋白紊乱如弹性皮肤松弛症中观察到 LOXL1 表达降低，而在纤维化疾病如特发性肺纤维化中报道表达增加。LOXL1 在假性剥脱性青光眼的筛板层中也下调，并且 LOXL1 基因中的遗传变异与假性剥脱性青光眼和假性剥脱综合征的发病风险增加有关。然而，在某些种族中，两个主要的风险等位基因是相反的，并且存在于很大一部分正常人群中，这表明复杂的遗传和环境调节参与了疾病的发病机制。似乎 LOXL1 内含子 1 中的非编码变异也可能参与 LOXL1 表达的调节。基因改变可能通过多种表观遗传和翻译后机制发生，如 DNA 甲基化、长非编码 RNA 和 microRNAs。这些可能是疾病治疗的未来靶点。环境因素，如缺氧、氧化应激和紫外线辐射暴露，改变 LOXL1 的表达，很可能是这些遗传和环境因素的组合影响疾病的发展和进展。在这篇综述中，我们详细讨论了 LOXL1 的特性、生物学作用和调节，重点讨论了假性剥脱综合征和青光眼。
