title: Fibulin-5 binds human smooth-muscle cells through alpha5beta1 and alpha4beta1 integrins, but does not support receptor activation.
abstract: Fibulin-5, an extracellular matrix glycoprotein expressed in elastin-rich tissues, regulates vascular cell behaviour and elastic fibre deposition. Recombinant full-length human fibulin-5 supported primary human aortic SMC (smooth-muscle cell) attachment through alpha5beta1 and alpha4beta1 integrins. Cells on fibulin-5 spread poorly and displayed prominent membrane ruffles but no stress fibres or focal adhesions, unlike cells on fibronectin that also binds these integrins. Cell migration and proliferation were significantly lower on fibulin-5 than on fibronectin. Treatment of cells on fibulin-5 with a beta1 integrin-activating antibody induced stress fibres, increased attachment, migration and proliferation, and stimulated signalling of epidermal growth factor receptor and platelet-derived growth factor receptors alpha and beta. Fibulin-5 also modulated fibronectin-mediated cell spreading and morphology. We have thus identified the beta1 integrins on primary SMCs that fibulin-5 interacts with, and have shown that failure of fibulin-5 to activate these receptors limits cell spreading, migration and proliferation.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Lomas
authors.forename: Kieran T
authors.initials: KT
authors.lastname: Mellody
authors.forename: Lyle J
authors.initials: LJ
authors.lastname: Freeman
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Bax
authors.forename: C Adrian
authors.initials: CA
authors.lastname: Shuttleworth
authors.forename: Cay M
authors.initials: CM
authors.lastname: Kielty
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D039041:Integrin alpha4beta1; D039081:Integrin alpha5beta1