title: Fibulin-4 and fibulin-5 in elastogenesis and beyond: Insights from mouse and human studies.
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.
authors.affiliation: Department of Molecular Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Papke
authors.affiliation: Department of Molecular Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA. Electronic address: hiromi.yanagisawa@utsouthwestern.edu.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yanagisawa
mesh_terms: D000818:Animals; D001011:Aorta / Q000196:embryology* / Q000378:metabolism; D004549:Elastin / Q000096:biosynthesis* / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C403672:EFEMP2 protein, human; D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D016023:Integrins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D004549:Elastin; D010447:Peptide Hydrolases
keywords: Aortic aneurysm; Collagen fibers; Cutis laxa; ECM; Elastic fibers; Integrin