Fibulin-5/DANCE is essential for elastogenesis in vivo

Tomoyuki Nakamura, Pilar Ruiz Lozano, Yasuhiro Ikeda, Yoshitaka Iwanaga, Aleksander Hinek, Susumu Minamisawa, Ching Feng Cheng, Kazuhiro Kobuke, Nancy Dalton, Yoshikazu Takada, Kei Tashiro, John Ross, Tasuku Honjo, Kenneth R. Chien

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Abstract

The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin1,2. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (0TGF)-β-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand3, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins αvβ3, αvβ5 and α9β1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature.

Original languageEnglish
Pages (from-to)171-175
Number of pages5
JournalNature
Volume415
Issue number6868
DOIs
Publication statusPublished - Jan 10 2002
Externally publishedYes

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ASJC Scopus subject areas

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Cite this

Nakamura, T., Lozano, P. R., Ikeda, Y., Iwanaga, Y., Hinek, A., Minamisawa, S., Cheng, C. F., Kobuke, K., Dalton, N., Takada, Y., Tashiro, K., Ross, J., Honjo, T., & Chien, K. R. (2002). Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature, 415(6868), 171-175. https://doi.org/10.1038/415171a