Role of transforming growth factor-β1 pathway in carbon nanotube stimulated collagen production in human lung cells

Details

• Personal Author:
  Castranova, Vincent ; Derk R ; Mishra A ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L ; Yuan J
• Description:
  Accumulated studies have shown that carbon nanotubes (CNT) induce rapid and progressive lung fibrosis in animal models but the mechanisms are not clear. Following CNT exposure transforming growth factor beta (TGF-beta), a pro-fibrogenic mediator, was induced both in vivo and in vitro models and was correlated with in vivo fibrosis and in vitro collagen induction. To understand the signaling mechanism of this fibrogenic response, we investigated the contribution of TGF-beta signaling in CNT-induced collagen production, a hall mark of fibrosis, using cultured human lung cells and determined the role of TGF-beta receptor-Smad (TGF-betaR1-Smad) signaling as a potential mechanism for CNT-induced fibrosis. Human lung epithelial (BEAS2B) cells and fibroblast (CRL1490) cells were exposed to doses relevant to in vivo exposure (0.02-0.6 microg/cm2 in vitro approximately 10-80 micorg/mouse lung) of well characterized and dispersed multi-walled CNT (MWCNT), single walled CNT (SWCNT) and ultrafine carbon black (UFCB). Protein expression was measured by immunofluorescence, western blotting and ELISA. Present results indicate: 1) CNT exposure caused induction of TGF-beta1 production in lung epithelial cells; 2) TGF-beta, TGF-betaR1, p-Smad-2, and collagen type I were overexpressed in CNTexposed fibroblast cells; 3) collagen I stimulating effects of MWCNT were partially blocked in TGF-betaR1 and Smad-2 knockdown fibroblast cells. In conclusion, CNT stimulate lung fibroblasts to induce collagen I in vitro through activation of the TGF-beta R1-Smad Signaling pathway. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Cytotoxins Environmental Monitoring Growth Immune System Laboratories Lung Occupational Health Respiratory System Safety Toxicology

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• Keywords:
  Analytical-instruments Cell-cultures Cytotoxic-effects Dose-response Exposure-assessment Exposure-levels Fibrogenicity Growth-factors Immune-reaction In-vitro-studies In-vivo-studies Laboratory-techniques Lung-cells Lung-fibrosis Measurement-equipment Molecular-biology Nanotechnology Proteins

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  96
• Volume:
  132
• Issue:
  1
• NIOSHTIC Number:
  nn:20042397
• Citation:
  Toxicologist 2013 Mar; 132(1):96
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Carbon black (CAS RN 1333-86-4)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:529cdf03cdf181037205b5aa59ac2f2697289b4bb1a43dca5caa4945e6445384875d3e04d848024b98e19bec90d52bdf5e84ff0992ead62d59fb427be8064bff
• Download URL:
  https://stacks.cdc.gov/view/cdc/194629/cdc_194629_DS1.pdf
• File Type:
  [PDF - 581.48 KB ]