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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aorta / embryology*
  • Aorta / metabolism
  • Elastin / biosynthesis*
  • Elastin / metabolism*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Expression Regulation, Enzymologic / physiology*
  • Humans
  • Integrins / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / immunology
  • Myocytes, Smooth Muscle / metabolism
  • Peptide Hydrolases / metabolism
  • Signal Transduction / physiology*

Substances

  • EFEMP2 protein, human
  • Extracellular Matrix Proteins
  • FBLN5 protein, human
  • Integrins
  • MIRN29a microRNA, human
  • MicroRNAs
  • Elastin
  • Peptide Hydrolases