Nature Genetics36, 178 - 182 (2004)
Published online: 25 January 2004; | doi:10.1038/ng1297
Elastic fiber homeostasis requires lysyl oxidase−like 1 protein
Xiaoqing Liu1, Yun Zhao1, Jiangang Gao2, Basil Pawlyk1, Barry Starcher3, Jeffrey A Spencer4, Hiromi Yanagisawa4, Jian Zuo2
& Tiansen Li1
1
Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School and Massachusetts Eye & Ear Infirmary, Boston, Massachusetts 02114, USA.
2
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
3
Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, Texas 75708, USA.
4
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Elastic fibers are components of the extracellular matrix and confer resilience1. Once laid down, they are thought to remain stable2, except in the uterine tract where cycles of active remodeling occur3. Loss of elastic fibers underlies connective tissue aging and important diseases including emphysema4,
5,
6,
7. Failure to maintain elastic fibers is explained by a theory of antielastase-elastase imbalance8, 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.
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