Role of transforming growth factor-ß1 pathway in carbon nanotube stimulated collagen production in human lung cells.
Mishra-A; Stueckle-TA; Derk-R; Castranova-V; Rojanasakul-Y; Yuan-J; Wang-L
Toxicologist 2013 Mar; 132(1):96
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 ~ 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.
Toxicology; Nanotechnology; Dose-response; Cytotoxic-effects; Growth-factors; Lung-cells; Lung-fibrosis; Cell-cultures; Molecular-biology; Immune-reaction; Fibrogenicity; In-vitro-studies; In-vivo-studies; Exposure-assessment; Exposure-levels; Proteins; Measurement-equipment; Laboratory-techniques; Analytical-instruments
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas