title: Periostin regulates fibrocyte function to promote myofibroblast differentiation and lung fibrosis.
abstract: Fibrocytes are circulating mesenchymal precursors (CD45+, col 1+) recruited to fibrotic areas. Fibrocytes secrete profibrotic mediators including periostin; a matricellular protein that regulates cellular interactions with extracellular matrix (ECM) components. In bleomycin-induced fibrosis, periostin deficiency in structural or hematopoietic cells limits development of pulmonary fibrosis. To determine if hematopoietic-derived fibrocytes might secrete soluble factors to activate structural myofibroblast differentiation, wild-type (WT) fibroblasts were treated with conditioned medium from fibrocytes isolated from bleomycin-treated WT or periostin-/-mice. After 24 h we saw less α-smooth muscle actin expression in cells treated with conditioned medium from periostin-/-fibrocytes. Adoptive transfer of WT fibrocytes augmented lung fibrosis to a greater extent than transfer of fibrocytes from periostin-/-mice. In vitro analysis of fibrocytes and fibroblasts isolated from WT and periostin-/-mice treated with TGFβ1 or periostin demonstrated co-regulation of mesenchymal activation and beta 1 integrin as a potential receptor for periostin on fibrocytes. Additionally, connective tissue growth factor (CTGF) mRNA expression was increased in fibrocytes treated with periostin whereas CTGF and lysl oxidase (LOX) mRNA expression was low in bleomycin-treated periostin-/-fibrocytes. These data suggest fibrocytes may augment bleomycin-induced fibrosis via secretion of periostin and other soluble factors that promote myofibroblast differentiation.
authors.affiliation: Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Ashley
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Wilke
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.|Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Moore
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001761:Bleomycin; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058628:Myofibroblasts / Q000502:physiology*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology*
chemical_list: C526318:CCN2 protein, mouse; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; C082838:Postn protein, mouse; D001761:Bleomycin; D055513:Connective Tissue Growth Factor; C077112:Lox protein, mouse; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase