Pleural mesothelial cell differentiation and invasion in fibrogenic lung injury

Details

• Personal Author:
  Agarwal A ; Antony VB ; Bolisetty S ; Ding Q ; Guroji P ; Hock T ; Jagirdar R ; Karki S ; Liu R-M ; Oliva O ; Surolia R ; Thannickal VJ ; Zolak JS
• Description:
  The origin of the myofibroblast in fibrotic lung disease is uncertain, and no effective medical therapy for fibrosis exists. We have previously demonstrated that transforming growth factor-β1 (TGF-β1) induces pleural mesothelial cell (PMC) transformation into myofibroblasts and haptotactic migration in vitro. Whether PMC differentiation and migration occurs in vivo, and whether this response can be modulated for therapeutic benefit, is unknown. Here, using mice recombinant for green fluorescent protein (GFP) driven by the Wilms tumor-1 (WT-1) promoter, we demonstrate PMC trafficking into the lung and differentiation into myofibroblasts. Carbon monoxide or the induction of heme oxygenase-1 (HO-1) inhibited the expression of myofibroblast markers, contractility, and haptotaxis in PMCs treated with TGF-β1. Intrapleural HO-1 induction inhibited PMC migration after intratracheal fibrogenic injury. PMCs from patients with idiopathic pulmonary fibrosis (IPF) exhibited increased expression of myofibroblast markers and enhanced contractility and haptotaxis, compared with normal PMCs. Carbon monoxide reversed this IPF PMC profibrotic phenotype. WT-1-expressing cells were present within fibrotic regions of the lungs in IPF subjects, supporting a role for PMC differentiation and trafficking as contributors to the myofibroblast population in lung fibrosis. Our findings also support a potential role for pleural-based therapies to modulate pleural mesothelial activation and parenchymal fibrosis progression. [Description provided by NIOSH]
• Subjects:
  Biomarkers Growth Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Cell-differentiation Cell-migration Cell-transformation Cellular-reactions Fibrogenicity Growth-factors Laboratory-animals Lung-cells Lung-disorders Lung-fibrosis Mesothelial-cells Pleural-cavity Proteins Pulmonary-system-disorders Respiratory-system-disorders Therapeutic-agents Tumor-inhibition

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• ISSN:
  0002-9440
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Alabama ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  182
• Issue:
  4
• NIOSHTIC Number:
  nn:20043131
• Citation:
  Am J Pathol 2013 Apr; 182(4):1239-1247
• Contact Point Address:
  Jason S. Zolak, M.D., Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, 1900 University Blvd., THT 422, Birmingham, AL 35294-0006
• Email:
  jasonzolak@gmail.com
• CAS Registry Number:
  Carbon monoxide (CAS RN 630-08-0)
• Federal Fiscal Year:
  2013
• Performing Organization:
  University of Alabama at Birmingham
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  The American Journal of Pathology
• End Date:
  20270630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d2ddfa2a0fc5eebf272a8b78bcdf57bdc92d6ba5f993bc6449fff3e3ccd6ff25b0697d30f96be2170a7e0f7456c088261371e4c8d2922db7031b366be248b6a3
• Download URL:
  https://stacks.cdc.gov/view/cdc/195135/cdc_195135_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]