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The Role Of Fibulin-1C Peptides In Attachment, Proliferation And ECM Deposition In Lung Fibroblasts From Chronic Lung Diseases
Rationale: Fibulin-1 is an extracellular matrix (ECM) protein which mediates cellular processes and tissue remodelling. In our previous study we have shown that the levels of fibulin-1 are elevated in serum and bronchoalveolar lavage fluid from asthmatic patients compared to healthy volunteers. Furthermore, in-vitro we found fibulin-1C, one of four fibulin-1 isoforms, promoted proliferation and wound repair in human airway smooth muscle cells.
Aim: To identify the bioactive regions of fibulin-1C which promote lung fibrosis induced by fibroblasts from patients with chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF) or neither disease (Non-C/P).
Methods: Fibulin-1C peptides were designed (seven in total) according to the principles described by Angelatti (1). The peptides were coated onto tissue culture plates before lung fibroblasts were seeded. The effects of peptides on fibroblast attachment, mitochondrial activity and proliferation, and ECM deposition were measured.
Results: Among the fibulin-1C peptides, peptide 1C1 (FBLN1C1) increased fibroblast attachment in Non-C/P and COPD, proliferation in Non-C/P, and mitochondrial activity in all three groups. In addition, FBLN1C1 enhanced fibulin1 deposition in COPD and PF fibroblasts, while it augmented fibronectin and perlecan deposition in all three groups of fibroblasts. The peptides FBLN1C2 to FBLN1C7 were inactive.
Conclusion: FBLN1C1 may be important in fibulin-1 induced lung fibrosis. The active peptide identified from this study will provide a useful tool for future studies in recognition of FBLN1C and receptor binding and exploration of cellular signalling pathways of FBLN1C. Further investigation of this molecule may help reveal the role of Fibulin-1 in the pathophysiology of chronic lung diseases.
History
Publication title
American Journal of Respiratory and Critical Care MedicineVolume
189Editors
Paul SchumackerISSN
1073-449XDepartment/School
Tasmanian School of MedicinePublisher
American Thoracic SocietyPlace of publication
United StatesEvent title
American Thoracic Society 2014 International ConferenceEvent Venue
San DiegoDate of Event (Start Date)
2014-05-16Date of Event (End Date)
2014-05-21Repository Status
- Restricted