Fibulin-5/DANCE is essential for elastogenesis in vivo.
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.
Nakamura
Tomoyuki
T
UCSD-Salk Program in Molecular Medicine and the UCSD Institute of Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Lozano
Pilar Ruiz
PR
Ikeda
Yasuhiro
Y
Iwanaga
Yoshitaka
Y
Hinek
Aleksander
A
Minamisawa
Susumu
S
Cheng
Ching-Feng
CF
Kobuke
Kazuhiro
K
Dalton
Nancy
N
Takada
Yoshikazu
Y
Tashiro
Kei
K
Ross
John
J
Honjo
Tasuku
T
Chien
Kenneth R
KR
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
D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; C120769:Fbln5 protein, mouse; D016023:Integrins; D011994:Recombinant Proteins; D004549:Elastin