Liu Xiaoqing, Zhao Yun, Gao Jiangang, Pawlyk Basil, Starcher Barry, Spencer Jeffrey A, Yanagisawa Hiromi, Zuo Jian, Li Tiansen
Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School and Massachusetts Eye & Ear Infirmary, Boston, Massachusetts 02114, USA.
Nat Genet. 2004 Feb;36(2):178-82. doi: 10.1038/ng1297. Epub 2004 Jan 25.
Elastic fibers are components of the extracellular matrix and confer resilience. Once laid down, they are thought to remain stable, except in the uterine tract where cycles of active remodeling occur. Loss of elastic fibers underlies connective tissue aging and important diseases including emphysema. Failure to maintain elastic fibers is explained by a theory of antielastase-elastase imbalance, but little is known about the role of renewal. Here we show that mice lacking the protein lysyl oxidase-like 1 (LOXL1) do not deposit normal elastic fibers in the uterine tract post partum and develop pelvic organ prolapse, enlarged airspaces of the lung, loose skin and vascular abnormalities with concomitant tropoelastin accumulation. Distinct from the prototypic lysyl oxidase (LOX), LOXL1 localizes specifically to sites of elastogenesis and interacts with fibulin-5. Thus elastin polymer deposition is a crucial aspect of elastic fiber maintenance and is dependent on LOXL1, which serves both as a cross-linking enzyme and an element of the scaffold to ensure spatially defined deposition of elastin.
弹性纤维是细胞外基质的组成部分，赋予组织弹性。一旦形成，它们通常被认为是稳定的，除了子宫组织会发生周期性的活跃重塑。弹性纤维的丧失是结缔组织衰老和包括肺气肿在内的重要疾病的基础。抗弹性蛋白酶-弹性蛋白酶失衡理论解释了弹性纤维维持失败的原因，但关于弹性纤维更新的作用知之甚少。在这里，我们表明，缺乏赖氨酰氧化酶样蛋白1（LOXL1）的小鼠产后子宫组织中无法沉积正常的弹性纤维，并出现盆腔器官脱垂、肺部气腔扩大、皮肤松弛和血管异常，同时伴有原弹性蛋白积累。与典型的赖氨酰氧化酶（LOX）不同，LOXL1特异性定位于弹性纤维生成部位，并与纤维连接蛋白-5相互作用。因此，弹性蛋白聚合物沉积是弹性纤维维持的关键方面，并且依赖于LOXL1，它既是一种交联酶，也是支架的一个组成部分，以确保弹性蛋白在空间上的特定沉积。
