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

Fingerprint

Fibroblasts
Endocytosis
Phosphotransferases
Lung
Carbon Nanotubes
Carbon nanotubes
Phosphorylation
Amiloride
Macrophages
Crosstalk
Epidermal Growth Factor
Collagen
Rodentia
Intercellular Signaling Peptides and Proteins
Pneumonia
Fibrosis
Epithelial Cells

Keywords

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

Cite this

Vietti, Giulia ; Ibouraadaten, Saloua ; Palmai-Pallag, Mihaly ; Yakoub, Yousof ; Piret, Jean Pascal ; Marbaix, Etienne ; Lison, Dominique ; Van Den Brule, Sybille. / Towards predicting the lung fibrogenic activity of MWCNT : Key role of endocytosis, kinase receptors and ERK 1/2 signaling. In: Nanotoxicology. 2016 ; Vol. 10, No. 4. pp. 488-500.
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Vietti, G, Ibouraadaten, S, Palmai-Pallag, M, Yakoub, Y, Piret, JP, 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, vol. 10, no. 4, pp. 488-500. https://doi.org/10.3109/17435390.2015.1088588

Towards predicting the lung fibrogenic activity of MWCNT : Key role of endocytosis, kinase receptors and ERK 1/2 signaling. / Vietti, Giulia; Ibouraadaten, Saloua; Palmai-Pallag, Mihaly; Yakoub, Yousof; Piret, Jean Pascal; Marbaix, Etienne; Lison, Dominique; Van Den Brule, Sybille.

In: Nanotoxicology, Vol. 10, No. 4, 20.04.2016, p. 488-500.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Towards predicting the lung fibrogenic activity of MWCNT

T2 - Key role of endocytosis, kinase receptors and ERK 1/2 signaling

AU - Vietti, Giulia

AU - Ibouraadaten, Saloua

AU - Palmai-Pallag, Mihaly

AU - Yakoub, Yousof

AU - Piret, Jean Pascal

AU - Marbaix, Etienne

AU - Lison, Dominique

AU - Van Den Brule, Sybille

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Y1 - 2016/4/20

N2 - 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.

AB - 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.

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KW - fibroblast proliferation

KW - growth factor

KW - lung fibrosis

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