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

Christina L. Papke, Hiromi Yanagisawa

Research output: Contribution to journalReview article

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)142-149
Number of pages8
JournalMatrix Biology
Volume37
DOIs
StatePublished - Jul 1 2014

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology

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