Towards predicting the lung fibrogenic activity of MWCNT: Key role of endocytosis, kinase receptors and ERK 1/2 signaling

Giulia Vietti, Saloua Ibouraadaten, Mihaly Palmai-Pallag, Yousof Yakoub, Jean Pascal Piret, Etienne Marbaix, Dominique Lison, Sybille Van Den Brule

Research output: Contribution to journalArticle

Abstract

Carbon nanotubes (CNT) have been reported to induce lung inflammation and fibrosis in rodents. We investigated the direct and indirect cellular mechanisms mediating the fibrogenic activity of multi-wall (MW) CNT on fibroblasts. We showed that MWCNT indirectly stimulate lung fibroblast (MLg) differentiation, via epithelial cells and macrophages, whereas no direct effect of MWCNT on fibroblast differentiation or collagen production was detected. MWCNT directly stimulated the proliferation of fibroblasts primed with low concentrations of growth factors, such as PDGF, TGF-β or EGF. MWCNT prolonged ERK 1/2 phosphorylation induced by low concentrations of PDGF or TGF-β in fibroblasts. This phenomenon and the proliferative activity of MWCNT on fibroblasts was abrogated by the inhibitors of ERK 1/2, PDGF-, TGF-β- and EGF-receptors. This activity was also reduced by amiloride, an endocytosis inhibitor. Finally, the lung fibrotic response to several MWCNT samples (different in length and diameter) correlated with their in vitro capacity to stimulate the proliferation of fibroblasts and to prolong ERK 1/2 signaling in these cells. Our findings point to a crosstalk between MWCNT, kinase receptors, ERK 1/2 signaling and endocytosis which stimulates the proliferation of fibroblasts. The mechanisms of action identified in this study contribute to predict the fibrogenic potential of MWCNT.

Original languageEnglish
Pages (from-to)488-500
Number of pages13
JournalNanotoxicology
Volume10
Issue number4
DOIs
Publication statusPublished - 20 Apr 2016

Keywords

  • Carbon nanotube
  • fibroblast proliferation
  • growth factor
  • lung fibrosis

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    Vietti, G., Ibouraadaten, S., Palmai-Pallag, M., Yakoub, Y., Piret, J. P., Marbaix, E., Lison, D., & Van Den Brule, S. (2016). Towards predicting the lung fibrogenic activity of MWCNT: Key role of endocytosis, kinase receptors and ERK 1/2 signaling. Nanotoxicology, 10(4), 488-500. https://doi.org/10.3109/17435390.2015.1088588