Elastic fiber homeostasis requires lysyl oxidase-like 1 protein
Elastic fiber homeostasis requires lysyl oxidase-like 1 protein
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DOI：
10.1038/ng1297
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发表时间：
2004-02-01
期刊：
影响因子：
30.8
通讯作者：
Li, TS
中科院分区：
文献类型：
--
作者：
Liu, XQ;Zhao, Y;Li, TS
弹性纤维是细胞外基质的组成部分，赋予弹性(1)。一旦奠定，它们被认为是保持稳定的(2)，除了在子宫道活跃重塑周期发生(3)。弹性纤维的丧失是结缔组织老化和包括肺气肿在内的重要疾病的基础（4-7）。不能保持弹性纤维是由反弹性酶-弹性酶失衡理论解释的(8)，但对更新的作用知之甚少。本研究表明，缺乏赖氨酸氧化酶样1 （LOXL1）的小鼠在产后不能在子宫内沉积正常的弹性纤维，并出现盆腔器官脱垂、肺空间扩大、皮肤松弛和血管异常，并伴有对弹力蛋白的积累。与原型赖氨酸氧化酶（LOX）不同，LOXL1特异性定位于弹性发生位点并与纤维蛋白-5相互作用。因此，弹性蛋白聚合物沉积是弹性纤维维持的一个关键方面，它依赖于LOXL1， LOXL1既是交联酶又是支架元件，以确保弹性蛋白在空间上的沉积。
Elastic fibers are components of the extracellular matrix and confer resilience(1). Once laid down, they are thought to remain stable(2), except in the uterine tract where cycles of active remodeling occur(3). Loss of elastic fibers underlies connective tissue aging and important diseases including emphysema(4-7). Failure to maintain elastic fibers is explained by a theory of antielastase-elastase imbalance(8), 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.