Multi-Walled Carbon Nanotubes Inhibit Estrogen Receptor Expression In Vivo and In Vitro Through Transforming Growth Factor beta1

Details

• Personal Author:
  Das D ; Moreno S ; Orandle M ; Porter DW ; Robinson S ; Sabo-Attwood T ; Saleh NB ; Smith LC
• Description:
  Exposure to multi-walled carbon nanotubes (MWCNTs) is suspected to contribute to pulmonary fibrosis through modulation of transforming growth factor beta1 (TGF-β1). There is growing evidence that estrogen signaling is important in pulmonary function and modulates pro-fibrogenic signaling in multiple models of pulmonary fibrosis, however an interaction between MWCNT exposure and estrogen signaling in the lung is not known. The purpose of this work was to determine whether estrogen signaling in the lung is a target for MWCNTs and to identify potential signaling mechanisms mediating MWCNT-induced responses using a whole-body inhalation mouse model and an in vitro human lung cell model. Mice exposed to MWCNTs had reduced mRNA expression of estrogen receptor alpha and beta (Esr1 and Esr2, respectively) in lung tissue at multiple time-points post exposure, whereas expression of G-protein coupled estrogen receptor 1 (Gper1) was more variable. We localized ESR1 protein expression as primarily associated with bronchioles and within inflammatory macrophages. The reduction in estrogen receptor expression was concomitant to an increase in TGF-β1 levels in the bronchoalveolar lavage fluid (BALF) of MWCNT-exposed animals. We confirmed a role for TGF-β1 in mediating MWCNT-induced repression of ESR1 mRNA expression using a TGF-β type-I receptor inhibitor in bronchial epithelial cells in vitro. Overall these results highlight a novel mechanism of MWCNT-induced signaling where MWCNT-induced regulation of TGF-β1 represses estrogen receptor expression. Dysregulated estrogen signaling through altered receptor expression may have potential consequences on lung function. [Description provided by NIOSH]
• Subjects:
  Coal Dust Explosions Mining Occupational Health Safety
• Keywords:
  Animals Author Keywords: Multi-walled Carbon Nanotube Estrogen Receptor Estrogens Exposure Levels Fibrosis Growth Factors In Vitro Study In Vivo Study Laboratory Animals Lung Lung Cells Models Multi-walled Carbon Nanotubes MWCNT Proteins Psychomotor Function Pulmonary System Disorders Respiratory System Disorders Risk Factors Transforming Growth Factor Beta1

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• ISSN:
  2452-0748
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Florida ; OSHA Region 3 ; OSHA Region 4 ; 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
• Volume:
  14
• NIOSHTIC Number:
  nn:20055349
• Citation:
  NanoImpact 2019 Feb; 14:100152
• Contact Point Address:
  Tara Sabo-Attwood, Center for Environmental and Human Toxicology, University of Florida, Gainesville; FL
• Email:
  sabo@phhp.ufl.edu
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  NanoImpact
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3ba4c5893d378909f0e3f6662a4e7add1a7e61b65b8aff7b69ae68d3d172e69aa1bd032d975a662b0c2dcee8416bb533b80fbd6f5e68503db65a5f75edacd079
• Download URL:
  https://stacks.cdc.gov/view/cdc/217678/cdc_217678_DS1.pdf
• File Type:
  [PDF - 1.17 MB ]