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Matrix Biol. 2014 Jul;37:142-9. doi: 10.1016/j.matbio.2014.02.004. Epub 2014 Mar 6.

Fibulin-4 and fibulin-5 in elastogenesis and beyond: Insights from mouse and human studies.

Author information

1
Department of Molecular Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA.
2
Department of Molecular Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA. Electronic address: hiromi.yanagisawa@utsouthwestern.edu.

Abstract

The fibulin family of extracellular matrix/matricellular proteins is composed of long fibulins (fibulin-1, -2, -6) and short fibulins (fibulin-3, -4, -5, -7) and is involved in protein-protein interaction with the components of basement membrane and extracellular matrix proteins. Fibulin-1, -2, -3, -4, and -5 bind the monomeric form of elastin (tropoelastin) in vitro and fibulin-2, -3, -4, and -5 are shown to be involved in various aspects of elastic fiber development in vivo. In particular, fibulin-4 and -5 are critical molecules for elastic fiber assembly and play a non-redundant role during elastic fiber formation. Despite manifestation of systemic elastic fiber defects in all elastogenic tissues, fibulin-5 null (Fbln5(-/-)) mice have a normal lifespan. In contrast, fibulin-4 null (Fbln4(-/-)) mice die during the perinatal period due to rupture of aortic aneurysms, indicating differential functions of fibulin-4 and fibulin-5 in normal development. In this review, we will update biochemical characterization of fibulin-4 and fibulin-5 and discuss their roles in elastogenesis and outside of elastogenesis based on knowledge obtained from loss-of-function studies in mouse and in human patients with FBLN4 or FBLN5 mutations. Finally, we will evaluate therapeutic options for matrix-related diseases.

KEYWORDS:

Aortic aneurysm; Collagen fibers; Cutis laxa; ECM; Elastic fibers; Integrin

PMID:
24613575
PMCID:
PMC4156930
DOI:
10.1016/j.matbio.2014.02.004
[Indexed for MEDLINE]
Free PMC Article

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