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 α5β1 and α4β1 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 β1 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 α and β. Fibulin-5 also modulated fibronectin-mediated cell spreading and morphology. We have thus identified the β1 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.
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August 2007
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Research Article|
July 13 2007
Fibulin-5 binds human smooth-muscle cells through α5β1 and α4β1 integrins, but does not support receptor activation
Amanda C. Lomas;
Amanda C. Lomas
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Kieran T. Mellody;
Kieran T. Mellody
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Lyle J. Freeman;
Lyle J. Freeman
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Daniel V. Bax;
Daniel V. Bax
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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C. Adrian Shuttleworth;
C. Adrian Shuttleworth
1
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
1Correspondence should be addressed to either of these authors (email [email protected] and [email protected]).
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Cay M. Kielty
Cay M. Kielty
1
1Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
1Correspondence should be addressed to either of these authors (email [email protected] and [email protected]).
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Publisher: Portland Press Ltd
Received:
March 22 2007
Revision Received:
April 25 2007
Accepted:
May 02 2007
Accepted Manuscript online:
May 02 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem J (2007) 405 (3): 417–428.
Article history
Received:
March 22 2007
Revision Received:
April 25 2007
Accepted:
May 02 2007
Accepted Manuscript online:
May 02 2007
Citation
Amanda C. Lomas, Kieran T. Mellody, Lyle J. Freeman, Daniel V. Bax, C. Adrian Shuttleworth, Cay M. Kielty; Fibulin-5 binds human smooth-muscle cells through α5β1 and α4β1 integrins, but does not support receptor activation. Biochem J 1 August 2007; 405 (3): 417–428. doi: https://doi.org/10.1042/BJ20070400
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