Carbon Nanotubes and Crystalline Silica Induce Matrix Remodeling and Contraction by Stimulating Myofibroblast Transformation in a Three-Dimensional Culture of Human Pulmonary Fibroblasts: Role of Dimension and Rigidity

Details

• Personal Author:
  Hindman B ; Ma Q
• Description:
  Pulmonary fibrosis is a poorly understood pathologic condition. Carbon nanotubes (CNTs) are nanomaterials with potentials for broad applications. CNTs can induce pulmonary fibrosis in animals, a cause for concern for exposed workers and consumers. Given the large number of CNTs available on the market and the seemingly infinite number of ways these particles can be modified in ways that may affect toxicity, in vitro models that can be used to quickly and effectively investigate the relative fibrogenicity of CNTs are much needed. Here we analyzed the fibrogenic potentials of six CNTs of varying physical properties and crystalline silica using two- and three-dimensional (2D and 3D, respectively) in vitro models. WI38-VA13 human pulmonary fibroblasts were treated with CNTs or silica, with TGF-B1, a known inducer of fibroblast differentiation, as positive control. The cells were examined for fibrotic matrix alterations, including myofibroblast transformation, matrix remodeling, and matrix contraction. While all tested CNTs induced myofibroblast differentiation in 2D and 3D cultures, the 3D culture allowed the examination of myofibroblast clustering, collagen deposition and rearrangement, cell division, and matrix contraction in response to fibrogenic exposures, processes critical for fibrosis in vivo. At 1 ug/ml, MWCNTs elicit higher induction of myofibroblast differentiation and matrix remodeling than SWCNTs. Among MWCNTs, those with the highest and lowest aspect ratios produced the largest effects, which were comparable to those by TGF-B1 and higher than those by silica. Thus, the 3D collagen-based model enables the study of matrix fibrotic processes induced by CNTs and silica particles directly and effectively. [Description provided by NIOSH]
• Subjects:
  Fibrosis Laboratories Lung Diseases Occupational Health Particulate Matter Respiratory Tract Diseases Safety Silicon Dioxide Toxicology
• Keywords:
  3D Culture Author Keywords: CNT Carbon Nanotubes CNT Crystalline Silica Fibroblasts In Vitro Study Laboratory Animals Matrix Remodeling Myofibroblast Nanotoxicology Particulates Pulmonary System Disorders Silica

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• ISSN:
  0340-5761
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  92
• Issue:
  11
• NIOSHTIC Number:
  nn:20053136
• Citation:
  Arch Toxicol 2018 Nov; 92(11):3291-3305
• Contact Point Address:
  Qiang Ma, Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505
• Email:
  qam1@cdc.gov
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6) ; Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Archives of Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dee3fbd7090702a4fd30e01e91758a4c671d70cfa30ce5862c4a7fc05bf77c635f5ffe8efee105c6b66d7a2f0f0706d50a04420bd766d98589afa9ac001b79c2
• Download URL:
  https://stacks.cdc.gov/view/cdc/215953/cdc_215953_DS1.pdf
• File Type:
  [PDF - 3.10 MB ]