title: The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts.
abstract: Prompt deposition of fibronectin-rich extracellular matrix is a critical feature of normal development and the host-response to injury. Fibronectin isoforms that include the EDA and EDB domains are prominent in these fibronectin matrices. We now report using human dermal fibroblast cultures that the EDA domain of fibronectin or EDA-derived peptides modeled after the C-C' loop promote stress fiber formation and myosin-light chain phosphorylation. These changes are accompanied by an increase in fibronectin synthesis and fibrillogenesis. These effects are blocked by pretreating cells with either siRNA or blocking antibody to the α4 integrin. Our data indicate that the interaction between the α4β1 integrin and the EDA domain of fibronectin helps to drive tissue fibrosis by promoting a contractile phenotype and an increase in fibronectin synthesis and deposition.
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, United States.
authors.forename: Arti V
authors.initials: AV
authors.lastname: Shinde
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, United States.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Kelsh
authors.affiliation: VA Northern California Health Care System and Center for Musculoskeletal Health, Department of Internal Medicine, University of California - Davis School of Medicine, Sacramento, CA, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Peters
authors.affiliation: Division of Protein Chemistry, Institute for Protein Research, Osaka University, Osaka, Japan.
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Sekiguchi
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, United States.
authors.forename: Livingston
authors.initials: L
authors.lastname: Van De Water
authors.affiliation: Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, United States. Electronic address: mckeowp@mail.amc.edu.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: McKeown-Longo
mesh_terms: D001665:Binding Sites; D002448:Cell Adhesion; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000196:embryology; D018994:Myosin Light Chains / Q000378:metabolism; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012867:Skin / Q000166:cytology; D022502:Stress Fibers / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; C067625:FN1 protein, human; D005353:Fibronectins; D039041:Integrin alpha4beta1; D018994:Myosin Light Chains
keywords: Contractility; Fibronectin; Fibrosis; Rho kinase; Stress fibers; α4β1 integrin