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Identification Of The Active Region Of Fibulin1 In Remodelling And Inflammation In Lung Fibroblasts
Rationale: Fibulin-1 is an extracellular matrix (ECM) protein which mediates cellular process and tissue remodelling. In our previous research we have shown that the levels of fibulin-1 are elevated in serum and bronchoalveolar lavage fluid of 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: As is it not known which parts of the fibulin molecule are bioactive, we aimed to identify which regions of fibulin-1C promote remodelling and inflammation.
Methods: Several fibulin-1C peptides were designed according to the principles described by Angelatti(1). The peptides were either coated on to tissue culture plates before lung fibroblasts were seeded or added onto the cells in a soluble form. The effects of peptides on fibroblast attachment, proliferation, wound repair and pro-inflammatory cytokine release were measured.
Results: Among the fibulin-1C peptides, peptides 1C1 (FBLN1C1), when coated on the plates, increased fibroblast attachment (35%, p<0.05, n=8) and proliferation (10%, p<0.05, n=4). In contrast, soluble FBLN1C1 decreased cell proliferation (17%, p<0.05, n=9), had no effect on wound repair but enhanced interleukin-6 release (25%, p<0.05, n=8) by lung fibroblasts.
Conclusion: FBLN1C1 may be important in fibulin-1 induced remodelling and inflammation. Further investigation of this molecule and its receptor may help understand the role of fibulin-1 in the pathophysiology of chronic lung diseases.
History
Publication title
American Journal of Respiratory and Critical Care MedicineVolume
187Editors
Dr. Jacob I. SznajderISSN
1073-449XDepartment/School
Tasmanian School of MedicinePublisher
American Thoracic SocietyPlace of publication
United StatesEvent title
American Thoracic Society 2013 International ConferenceEvent Venue
Philadelphia PennsylvaniaDate of Event (Start Date)
2013-05-17Date of Event (End Date)
2013-05-22Repository Status
- Restricted