title: Fibulin-5/DANCE is essential for elastogenesis in vivo.
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 skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-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 ligand, 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 alphavbeta3, alphavbeta5 and alpha9beta1 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.
authors.affiliation: UCSD-Salk Program in Molecular Medicine and the UCSD Institute of Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakamura
authors.forename: Pilar Ruiz
authors.initials: PR
authors.lastname: Lozano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: Aleksander
authors.initials: A
authors.lastname: Hinek
authors.forename: Susumu
authors.initials: S
authors.lastname: Minamisawa
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobuke
authors.forename: Nancy
authors.initials: N
authors.lastname: Dalton
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takada
authors.forename: Kei
authors.initials: K
authors.lastname: Tashiro
authors.forename: John
authors.initials: J
authors.lastname: Ross
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
mesh_terms: D000818:Animals; D001011:Aorta / Q000196:embryology / Q000473:pathology; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003483:Cutis Laxa / Q000209:etiology; D004547:Elastic Tissue / Q000196:embryology* / Q000502:physiology / Q000648:ultrastructure; D004549:Elastin / Q000378:metabolism*; D004646:Emphysema / Q000209:etiology / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins
chemical_list: D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; C120769:Fbln5 protein, mouse; D016023:Integrins; D011994:Recombinant Proteins; D004549:Elastin