Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

Jaffar, Jade; Unger, Sofia; Corte, Tamera J.; Keller, Michael; Wolters, Paul J.; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M.; Hansbro, Philip M.; Argraves, W. Scott; Oliver, Rema A.; Oliver, Brian G.; Black, Judith L.; Burgess, Janette K.

doi:10.1378/chest.13-2688

Cited by 47 publications

(47 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This extends other observations in which Fbln1 was increased in the serum of asthma (13) and IPF patients (15), suggesting that Fbln1 may be a biomarker and therapeutic target in respiratory diseases and other conditions involving remodeling and inflammation.…”

Section: Discussionsupporting

confidence: 87%

“…Increased levels of Fbln1 occur in serum and bronchoalveolar lavage fluid (BALF) of asthma patients, and inhibition of Fbln1c expression by antisense oligonucleotide reduced the proliferation of ASM cells from these patients (13). In IPF, ECM proteins are increased in both plasma and lung tissue (15), and Fbln1c variant–specific peptide increases the proliferation of lung fibroblasts, the main producers of ECM, in COPD and IPF patients (14). Cytokines associated with lung diseases, such as TGF-β, that are known to induce ECM proteins (16) also stimulate Fbln1 production in ASM cells from COPD patients, further indicating roles for Fbln1 in airway remodeling (17).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases

Liu¹,

Cooley²,

Jarnicki³

et al. 2016

JCI Insight

Self Cite

116

161

View full text Add to dashboard Cite

Airway and/or lung remodeling, involving exaggerated extracellular matrix (ECM) protein deposition, is a critical feature common to pulmonary diseases including chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Fibulin-1 (Fbln1), an important ECM protein involved in matrix organization, may be involved in the pathogenesis of these diseases. We found that Fbln1 was increased in COPD patients and in cigarette smoke–induced (CS-induced) experimental COPD in mice. Genetic or therapeutic inhibition of Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-α, IL-33, and CXCL1) in experimental COPD. Fbln1c−/− mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases

Liu¹,

Cooley²,

Jarnicki³

et al. 2016

JCI Insight

Self Cite

116

161

View full text Add to dashboard Cite

show abstract

“…In our previous research we have found that the level of fibulin-1 is elevated in the serum and bronchoalveolar lavage fluid of patients with asthma compared to people without asthma, and serum and tissue fibulin-1 levels are increased in the patients with IPF compared to those without lung diseases1724. Furthermore we have found that gene silencing of FBLN1C reduced cell proliferation and wound healing of ASM cells and reduced features of lung disease in a murine model17.…”

mentioning

confidence: 92%

Fibulin1C peptide induces cell attachment and extracellular matrix deposition in lung fibroblasts

Chen

Jaffar

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Due to its established role in the pathophysiology of airway fibrosis in patients with chronic asthma, fibulin-1 was supposed to be involved in the mechanisms of fibrogenesis and progression of IPF through a dysregulated expression [79]. In a recent study, Jaffar et al [80] have shown that fibroblasts of IPF patients produce more fibulin-1. Serum and tissue levels of this protein were increased in IPF compared with controls and correlated negatively with lung function (FVC).…”

Section: Ecm Remodelling and Fibroproliferationmentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis: Molecular Endotypes of Fibrosis Stratifying Existing and Emerging Therapies

Magnini¹,

Montemurro²,

Iovene³

et al. 2017

Respiration

Self Cite

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown causes. Current diagnostic criteria are based on radiological, clinical, and histopathological features but, unfortunately, still many patients remain undiagnosed. Two currently approved therapies, pirfenidone and nintedanib, slow down disease progression but failed to block or revert it. On the other hand, many of the therapeutic agents tested in several clinical trials have not given satisfactory answers, probably due to the pathological heterogeneity of the disease. A growing number of studies show that IPF phenotype is the common clinical outcome of a variety of different pathophysiological mechanisms that identify disease subgroups characterised by specific genetic and molecular biomarkers (endotypes). The precision medicine approach is identifying and analysing the complex system of genetic, molecular, environmental, and behavioural variables underlying the development of the disease and the response to therapy. These molecular pathways are potential targets for novel agents and useful diagnostic, prognostic, and theragnostic biomarkers. We outline the status of knowledge in this field by discussing the complex pathogenetic pathways underlying different disease subgroups and assessing a stratification approach to novel therapeutic agents based on these endotypes.

show abstract

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

Cited by 47 publications

References 27 publications

Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases

Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases

Fibulin1C peptide induces cell attachment and extracellular matrix deposition in lung fibroblasts

Idiopathic Pulmonary Fibrosis: Molecular Endotypes of Fibrosis Stratifying Existing and Emerging Therapies

Contact Info

Product

Resources

About