Open AccessFibulin‐5, an integrin‐binding matricellular protein: its function in development and disease
Author(s) -
Yanagisawa Hiromi,
Schluterman Marie K.,
Brekken Rolf A.
Publication year - 2009
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-009-0065-3
Subject(s) - fibulin , matricellular protein , fibronectin , microbiology and biotechnology , extracellular matrix , angiogenesis , integrin , tropoelastin , elastin , ctgf , biology , chemistry , receptor , cancer research , biochemistry , growth factor , genetics
Interactions between the extracellular matrix (ECM) and cells are critical in embryonic development, tissue homeostasis, physiological remodeling, and tumorigenesis. Matricellular proteins, a group of ECM components, mediate cell‐ECM interactions. One such molecule, Fibulin‐5 is a 66‐kDa glycoprotein secreted by various cell types, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. Fibulin‐5 contributes to the formation of elastic fibers by binding to structural components including tropoelastin and fibrillin‐1, and to cross‐linking enzymes, aiding elastic fiber assembly. Mice deficient in the fibulin‐5 gene ( Fbln5 ) exhibit systemic elastic fiber defects with manifestations of loose skin, tortuous aorta, emphysematous lung and genital prolapse. Although Fbln5 expression is down‐regulated after birth, following the completion of elastic fiber formation, expression is reactivated upon tissue injury, affecting diverse cellular functions independent of its elastogenic function. Fibulin‐5 contains an evolutionally conserved arginine‐glycine‐aspartic acid (RGD) motif in the N‐terminal region, which mediates binding to a subset of integrins, including α5β1, αvβ3, and αvβ5. Fibulin‐5 enhances substrate attachment of endothelial cells, while inhibiting migration and proliferation in a cell type‐ and context‐dependent manner. The antagonistic function of fibulin‐5 in angiogenesis has been demonstrated in vitro and in vivo; fibulin‐5 may block angiogenesis by inducing the anti‐angiogenic molecule thrompospondin‐1, by antagonizing VEGF 165 ‐mediated signaling, and/or by antagonizing fibronectin‐mediated signaling through directly binding and blocking the α5β1 fibronectin receptor. The overall effect of fibulin‐5 on tumor growth depends on the balance between the inhibitory property of fibulin‐5 on angiogenesis and the direct effect of fibulin‐5 on proliferation and migration of tumor cells. However, the effect of tumor‐derived versus host microenvironment‐derived fibulin‐5 remains to be evaluated.