Journal article
Fibulin-1 is increased in asthma – A novel mediator of airway remodeling?
PloS one, Vol.5(10), e13360
2010
Abstract
Background
The extracellular matrix is a dynamic and complex network of macromolecules responsible for maintaining and influencing cellular functions of the airway. The role of fibronectin, an extracellular matrix protein, is well documented in asthma. However, the expression and function of fibulin-1, a secreted glycoprotein which interacts with fibronectin, has not been reported. Fibulin-1 is widely expressed in basement membranes in many organs including the lung. There are four isoforms in humans (A–D) of which fibulin-1C and 1D predominate. The objective of this study was to study the expression of fibulin-1 in volunteers with and without asthma, and to examine its function in vitro.
Methodology/Principal Findings
We used immunohistochemistry and dot-blots to examine fibulin-1 levels in bronchial biopsies, bronchoalveolar lavage fluid and serum. Real-time PCR for fibulin-1C and 1D, and ELISA and western blotting for fibulin-1 were used to study the levels in airway smooth muscle cells. The function of fibulin-1C was determined by assessing its role, using an antisense oligonucleotide, in cell proliferation, migration and wound healing. A murine model of airway hyperresponsiveness (AHR) was used to explore the biological significance of fibulin-1. Levels of fibulin-1 were significantly increased in the serum and bronchoalveolar lavage fluid of 21 asthmatics compared with 11 healthy volunteers. In addition fibulin-1 was increased in asthma derived airway smooth muscle cells and fibulin-1C contributed to the enhanced proliferation and wound repair in these cells. These features were reversed when fibulin-1C was suppressed using an antisense oligomer. In a mouse model of AHR, treatment with an AO inhibited the development of AHR to methacholine.
Conclusions
Our data collectively suggest fibulin-1C may be worthy of further investigation as a target for airway remodeling in asthma.
Details
- Title
- Fibulin-1 is increased in asthma – A novel mediator of airway remodeling?
- Authors/Creators
- Z. Zhou (Author/Creator)J.Y. Lau (Author/Creator) - Cooperative Research CentreB.G. Oliver (Author/Creator) - The University of SydneyM. Baraket (Author/Creator) - The University of SydneyE.L. Beckett (Author/Creator) - Hunter Medical Research InstituteN.G. Hansbro (Author/Creator)L.M. Moir (Author/Creator) - The University of SydneyS.D. Wilton (Author/Creator) - The University of Western AustraliaC. Williams (Author/Creator) - The University of Western AustraliaP.S. Foster (Author/Creator) - Hunter Medical Research InstituteP.M. Hansbro (Author/Creator) - Hunter Medical Research InstituteJ.L. Black (Author/Creator) - The University of SydneyJ.K. Burgess (Author/Creator) - Groningen Research Institute for Asthma and COPD (GRIAC)
- Publication Details
- PloS one, Vol.5(10), e13360
- Publisher
- Public Library of Science
- Identifiers
- 991005541944707891
- Copyright
- 2010 Lau et al.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.65 Allergy
- 1.65.44 Asthma
- Web Of Science research areas
- Respiratory System
- ESI research areas
- Clinical Medicine