title: Fibulin1C peptide induces cell attachment and extracellular matrix deposition in lung fibroblasts.
abstract: Fibulin-1 is an extracellular matrix (ECM) protein, levels of which are elevated in serum and lung tissue from patients with idiopathic pulmonary fibrosis compared to healthy volunteers. Inhibition of fibulin-1C, one of four fibulin-1 isoforms, reduced proliferation and wound healing in human airway smooth muscle (ASM) cells. This study identified the bioactive region/s of fibulin-1C which promotes fibrosis. Seven fibulin-1C peptides were synthesized and used to pre-coat tissue culture plates before lung derived ASM cells and fibroblasts from patients with pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD) or neither disease (Control) were plated. Peptide effects on in vitro measures of fibrosis: cell attachment, proliferation and viability, and ECM deposition, were examined. Among these peptides, peptide 1C1 (FBLN1C1) enhanced ASM cell and fibroblast attachment. FBLN1C1 increased mitochondrial activity and proliferation in fibroblasts. In addition, FBLN1C1 stimulated fibulin1 deposition in PF and COPD fibroblasts, and augmented fibronectin and perlecan deposition in all three groups. Peptides FBLN1C2 to FBLN1C7 had no activity. The active fibulin-1C peptide identified in this study describes a useful tool for future studies. Ongoing investigation of the role of fibulin-1 may reveal the mechanisms underlying the pathphysiology of chronic lung diseases.
authors.affiliation: 1] Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia [2] Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia.
authors.forename: Jade
authors.initials: J
authors.lastname: Jaffar
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: William Scott
authors.initials: WS
authors.lastname: Argraves
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Waleed O
authors.initials: WO
authors.lastname: Twal
authors.affiliation: School of Biomedical Science and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Phil
authors.initials: P
authors.lastname: Hansbro
authors.affiliation: 1] Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia [2] Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
authors.forename: Judith L
authors.initials: JL
authors.lastname: Black
authors.affiliation: 1] Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia [2] Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.affiliation: 1] Respiratory Cellular and Molecular Biology Group, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia [2] Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia [3] School of Medical &Molecular Biosciences, University of Technology Sydney, Sydney, NSW 2000, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
mesh_terms: D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; C574442:extra domain A fibronectin, human; C060820:fibulin; C071927:perlecan
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