title: Resistin-like molecule-β (RELM-β) targets airways fibroblasts to effect remodelling in asthma: from mouse to man.
abstract: BACKGROUND
  RELM-β has been implicated in airways inflammation and remodelling in murine models. Its possible functions in human airways are largely unknown. The aim was to address the hypothesis that RELM-β plays a role in extracellular matrix deposition in asthmatic airways.
  
  
  METHODS
  The effects of RELM-β gene deficiency were studied in a model of allergen exposure in mice sensitised and challenged with Aspergillus fumigatus (Af). RELM-β expression was investigated in bronchial biopsies from asthmatic patients. Direct regulatory effects of RELM-β on human lung fibroblasts were examined using primary cultures and the MRC5 cell line in vitro.
  
  
  RESULTS
  Sensitisation and challenge of wild-type mice with Af-induced release of RELM-β with a time course coincident with that of procollagen in the airways. Af-induced expression of mRNA encoding some, but not all ECM in the lung parenchyma was attenuated in RELM-β-/- mice. RELM-β expression was significantly increased in the bronchial submucosa of human asthmatics compared with controls, and its expression correlated positively with that of fibronectin and α-smooth muscle actin. In addition to epithelial cells, macrophages, fibroblasts and vascular endothelial cells formed the majority of cells expressing RELM-β in the submucosa. Exposure to RELM-β increased TGF-β1, TGF-β2, collagen I, fibronectin, smooth muscle α-actin, laminin α1, and hyaluronan and proteoglycan link protein 1 (Hapl1) production as well as proliferation by human lung fibroblasts in vitro. These changes were associated with activation of ERK1/2 in MRC5 cells.
  
  
  CONCLUSIONS
  The data are consistent with the hypothesis that elevated RELM-β expression in asthmatic airways contributes to airways remodelling at least partly by increasing fibroblast proliferation and differentiation with resulting deposition of extracellular matrix proteins.
authors.affiliation: MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, The Department of Asthma, Allergy and Respiratory Science, King's College London, London, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Fang
authors.affiliation: Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases and Division of Pharmacology, School of Basic Medical Science, Hebei United University, Hebei, China.
authors.forename: L J
authors.initials: LJ
authors.lastname: Yin
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kierstein
authors.affiliation: MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, The Department of Asthma, Allergy and Respiratory Science, King's College London, London, UK.
authors.forename: H F
authors.initials: HF
authors.lastname: Wu
authors.affiliation: MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, The Department of Asthma, Allergy and Respiratory Science, King's College London, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Eid
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Haczku
authors.affiliation: MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, The Department of Asthma, Allergy and Respiratory Science, King's College London, London, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Corrigan
authors.affiliation: MRC & Asthma UK Centre for Allergic Mechanisms of Asthma, The Department of Asthma, Allergy and Respiratory Science, King's College London, London, UK.|The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Ying
mesh_terms: D000199:Actins / Q000378:metabolism; D056151:Airway Remodeling / Q000235:genetics / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
chemical_list: D000199:Actins; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; C486574:RETNLB protein, human; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; C121346:laminin 1; D003094:Collagen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: RELM-β; TGF-β; asthma; collagen; fibronectin; remodelling