Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-β-mediated Akt/GSK-3β/SNAIL-1 signalling pathway

Manuela Polimeni1, Giulia Rossana Gulino1, Elena Gazzano1, Joanna Kopecka1, Arianna Marucco2, Ivana Fenoglio2, Federico Cesano3, Luisa Campagnolo4, Andrea Magrini4, Antonio Pietroiusti4, Dario Ghigo2, Elisabetta Aldieri2
1Department of Oncology, University of Turin, via Santena 5/bis, 10126, Turin, Italy
2Interdepartmental Centre Scansetti for Studies on Asbestos and Other Toxic Particulates, University of Turin, Turin, Italy
3Department of Chemistry, University of Turin, Via Pietro Giuria 7, 10125, Turin, Italy
4Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy

Tóm tắt

Từ khóa


Tài liệu tham khảo

Eatemadi A, Daraee H, Karimkhanloo H, Kouhi M, Zarghami N, Akbarzadeh A, Abasi M, Hanifehpour Y, Joo SW. Carbon nanotubes: properties, synthesis, purification, and medical applications. Nanoscale Res Lett. 2014;9(1):393.

De Volder MF, Tawfick SH, Baughman RH, Hart AJ. Carbon nanotubes: present and future commercial applications. Science. 2013;339(6119):535.

Donaldson K, Poland CA, Murphy FA, MacFarlane M, Chernova T, Schinwald A. Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences. Adv Drug Deliv Rev. 2013;65(15):2078.

Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WA, Seaton A, Stone V, Brown S, Macnee W, Donaldson K. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat Nanotechnol. 2008;3(7):423.

Porter DW, Hubbs AF, Mercer RR, Wu N, Wolfarth MG, Sriram K, Leonard S, Battelli L, Schwegler-Berry D, Friend S, Andrew M, Chen BT, Tsuruoka S, Endo M, Castranova V. Mouse pulmonary dose- and time course-responses induced by exposure to multi-walled carbon nanotubes. Toxicology. 2010;269(2-3):136.

He X, Young SH, Schwegler-Berry D, Chisholm WP, Fernback JE, Ma Q. Multiwalled carbon nanotubes induce a fibrogenic response by stimulating reactive oxygen species production, activating NF-κB signaling, and promoting fibroblast-to-myofibroblast transformation. Chem Res Toxicol. 2011;24(12):2237.

Mercer RR, Hubbs AF, Scabilloni JF, Wang L, Battelli LA, Friend S, Castranova V, Porter DW. Pulmonary fibrotic response to aspiration of multi-walled carbon nanotubes. Part Fibre Toxicol. 2011;8:21.

Wang X, Xia T, Ntim SA, Ji Z, Lin S, Meng H, Chung CH, George S, Zhang H, Wang M, Li N, Yang Y, Castranova V, Mitra S, Bonner JC, Nel AE. Dispersal state of multiwalled carbon nanotubes elicits profibrogenic cellular responses that correlate with fibrogenesis biomarkers and fibrosis in the murine lung. ACS Nano. 2011;5(12):9772.

Takagi A, Hirose A, Futakuchi M, Tsuda H, Kanno J. Dose-dependent mesothelioma induction by intraperitoneal administration of multi-wall carbon nanotubes in p53 heterozygous mice. Cancer Sci. 2012;103(8):1440.

Wang P, Nie X, Wang Y, Li Y, Ge C, Zhang L, Wang L, Bai R, Chen Z, Zhao Y, Chen C. Multiwall carbon nanotubes mediate macrophage activation and promote pulmonary fibrosis through TGF-β/Smad signaling pathway. Small. 2013;9(22):3799.

Kido T, Tsunoda M, Kasai T, Sasaki T, Umeda Y, Senoh H, Yanagisawa H, Asakura M, Aizawa Y, Fukushima S. The increases in relative mRNA expressions of inflammatory cytokines and chemokines in splenic macrophages from rats exposed to multi-walled carbon nanotubes by whole-body inhalation for 13 weeks. Inhal Toxicol. 2014;26(12):750.

Kasai T, Umeda Y, Ohnishi M, Kondo H, Takeuchi T, Aiso S, Nishizawa T, Matsumoto M, Fukushima S. Thirteen-week study of toxicity of fiber-like multi-walled carbon nanotubes with whole-body inhalation exposure in rats. Nanotoxicology. 2014. doi: 10.3109/17435390.2014.933903 .

Rittinghausen S, Hackbarth A, Creutzenberg O, Ernst H, Heinrich U, Leonhardt A, Schaudien D. The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats. Part Fibre Toxicol. 2014;11(1):59.

Sargent LM, Porter DW, Staska LM, Hubbs AF, Lowry DT, Battelli L, Siegrist KJ, Kashon ML, Mercer RR, Bauer AK, Chen BT, Salisbury JL, Frazer D, McKinney W, Andrew M, Tsuruoka S, Endo M, Fluharty KL, Castranova V, Reynolds SH. Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes. Part Fibre Toxicol. 2014;11:3.

Snyder RJ, Hussain S, Rice AB, Garantziotis S. Multiwalled carbon nanotubes induce altered morphology and loss of barrier function in human bronchial epithelium at noncytotoxic doses. Int J Nanomedicine. 2014;9:4093.

Rotoli BM, Gatti R, Movia D, Bianchi MG, Di Cristo L, Fenoglio I, Sonvico F, Bergamaschi E, Prina-Mello A, Bussolati O. Identifying contact-mediated, localized toxic effects of MWCNT aggregates on epithelial monolayers: a single-cell monitoring toxicity assay. Nanotoxicology. 2014. doi: 10.3109/17435390.2014.918203 .

Hussain S, Sangtian S, Anderson SM, Snyder RJ, Marshburn JD, Rice AB, Bonner JC, Garantziotis S. Inflammasome activation in airway epithelial cells after multi-walled carbon nanotube exposure mediates a profibrotic response in lung fibroblasts. Part Fibre Toxicol. 2014;11:28.

Mishra A, Rojanasakul Y, Chen BT, Castranova V, Mercer RR, Wang LY. Assessment of pulmonary fibrogenic potential of multiwalled carbon nanotubes in human lung cells. J Nanomater. 2012; 2012(ID 930931). doi: 10.1155/2012/930931 .

Wang P, Wang Y, Nie X, Braïni C, Bai R, Chen C. Multiwall carbon nanotubes directly promote fibroblast-myofibroblast and epithelial-mesenchymal transitions through the activation of the TGF-β/Smad signaling pathway. Small. 2015;11(4):446.

Kumarathasan P, Breznan D, Das D, Salam MA, Siddiqui Y, Mackinnon-Roy C, Guan J, de Silva N, Simard B, Vincent R. Cytotoxicity of carbon nanotube variants: a comparative in vitro exposure study with A549 epithelial and J774 macrophage cells. Nanotoxicology. 2014. doi: 10.3109/17435390.2014.902519 .

Ju L, Zhang G, Zhang X, Jia Z, Gao X, Jiang Y, Yan C, Duerksen-Hughes PJ, Chen FF, Li H, Zhu X, Yang J. Proteomic analysis of cellular response induced by multi-walled carbon nanotubes exposure in A549 cells. PLoS One. 2014;9(1):e84974.

Chen T, Nie H, Gao X, Yang J, Pu J, Chen Z, Cui X, Wang Y, Wang H, Jia G. Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway. Toxicol Lett. 2014;226(2):150.

Willis BC, Borok Z. TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol. 2007;293(3):L525.

Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178.

Muhlfeld C, Poland CA, Duffin R, Brandenberger C, Murphy FA, Rothen-Rutishauser B, Gehr P, Donaldson K. Differential effects of long and short carbon nanotubes on the gas-exchange region of the mouse lung. Nanotoxicology. 2012;6:867.

Aldieri E, Fenoglio I, Cesano F, Gazzano E, Gulino G, Scarano D, Attanasio A, Mazzucco G, Ghigo D, Fubini B. The role of iron impurities in the toxic effects exerted by short multiwalled carbon nanotubes (MWCNT) in murine alveolar macrophages. J Toxicol Environ Health A. 2013;76(18):1056.

Fenoglio I, Aldieri E, Gazzano E, Cesano F, Colonna M, Scarano D, Mazzucco G, Attanasio A, Yakoub Y, Lison D, Fubini B. Thickness of multi-walled carbon nanotubes affects their lung toxicity. Chem Res Toxicol. 2012;25:74.

Nymark P, Jensen KA, Suhonen S, Kembouche Y, Vippola M, Kleinjans J, Catalán J, Norppa H, van Delft J, Briedé JJ. Free radical scavenging and formation by multi-walled carbon nanotubes in cell free conditions and in human bronchial epithelial cells. Part Fibre Toxicol. 2014;11:4.

Pardo A, Selman M. Matrix metalloproteases in aberrant fibrotic tissue remodeling. Proc Am Thorac Soc. 2006;3(4):383.

Scanlon CS, Van Tubergen EA, Inglehart RC, D’Silva NJ. Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma. J Dent Res. 2013;92(2):114.

Peinado H, Quintanilla M, Cano A. Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. J Biol Chem. 2003;278(23):21113.

Lan A, Qi Y, Du J. Akt2 mediates TGF-β1-induced epithelial to mesenchymal transition by deactivating GSK3β/snail signaling pathway in renal tubular epithelial cells. Cell Physiol Biochem. 2014;34(2):368.

Zavadil J, Böttinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 2005;24(37):5764.

Jope RS, Yuskaitis CJ, Beurel E. Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem Res. 2007;32(4-5):577.

Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M, Hung MC. Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 2004;6(10):931.

Lee YJ, Han HJ. Troglitazone ameliorates high glucose-induced EMT and dysfunction of SGLTs through PI3K/Akt, GSK-3β, Snail1, and β-catenin in renal proximal tubule cells. Am J Physiol Renal Physiol. 2010;298(5):F1263.

Kattla JJ, Carew RM, Heljic M, Godson C, Brazil DP. Protein kinase B/Akt activity is involved in renal TGF-beta1-driven epithelial-mesenchymal transition in vitro and in vivo. Am J Physiol Renal Physiol. 2008;295(1):F215.

Kasper M, Huber O, Grossmann H, Rudolph B, Tränkner C, Müller M. Immunocytochemical distribution of E-cadherin in normal and injured lung tissue of the rat. Histochem Cell Biol. 1995;104(5):383.

Kaarteenaho R, Lappi-Blanco E, Lehtonen S. Epithelial N-cadherin and nuclear β-catenin are up-regulated during early development of human lung. BMC Dev Biol. 2010;10:113.

Choi SJ, Oh JM, Choy JH. Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells. J Inorg Biochem. 2009;103(3):463.

Herzog E, Byrne HJ, Davoren M, Casey A, Duschl A, Oostingh GJ. Dispersion medium modulates oxidative stress response of human lung epithelial cells upon exposure to carbon nanomaterial samples. Toxicol Appl Pharmacol. 2009;236(3):276.

Shvedova AA, Pietroiusti A, Fadeel B, Kagan VE. Mechanisms of carbon nanotube-induced toxicity: focus on oxidative stress. Toxicol Appl Pharmacol. 2012;261(2):121.

Kato T, Totsuka Y, Ishino K, Matsumoto Y, Tada Y, Nakae D, Goto S, Masuda S, Ogo S, Kawanishi M, Yagi T, Matsuda T, Watanabe M, Wakabayashi K. Genotoxicity of multi-walled carbon nanotubes in both in vitro and in vivo assay systems. Nanotoxicology. 2012;7(4):452.

Shvedova AA, Kisin E, Murray AR, Johnson VJ, Gorelik O, Arepalli S, Hubbs AF, Mercer RR, Keohavong P, Sussman N, Jin J, Yin J, Stone S, Chen BT, Deye G, Maynard A, Castranova V, Baron PA, Kagan VE. Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Am J Physiol Lung Cell Mol Physiol. 2008;295(4):L552.

Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N, Kitajima S, Kanno J. Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci. 2008;33(1):105.

Xu J, Alexander DB, Futakuchi M, Numano T, Fukamachi K, Suzui M, Omori T, Kanno J, Hirose A, Tsuda H. Size- and shape-dependent pleural translocation, deposition, fibrogenesis, and mesothelial proliferation by multiwalled carbon nanotubes. Cancer Sci. 2014;105(7):763.

Ryman-Rasmussen JP, Cesta MF, Brody AR, Shipley-Phillips JK, Everitt JI, Tewksbury EW, Moss OR, Wong BA, Dodd DE, Andersen ME, Bonner JC. Inhaled carbon nanotubes reach the subpleural tissue in mice. Nat Nanotechnol. 2009;4(11):747.

Mercer RR, Hubbs AF, Scabilloni JF, Wang L, Battelli LA, Schwegler-Berry D, Castranova V, Porter DW. Distribution and persistence of pleural penetrations by multi-walled carbon nanotubes. Part Fibre Toxicol. 2010;7:28.

Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol. 2010;28(12):1300.

Chang CC, Tsai ML, Huang HC, Chen CY, Dai SX. Epithelial-mesenchymal transition contributes to SWCNT-induced pulmonary fibrosis. Nanotoxicology. 2012;6(6):600.

Tanjore H, Xu XC, Polosukhin VV, Degryse AL, Li B, Han W, Sherrill TP, Plieth D, Neilson EG, Blackwell TS, Lawson WE. Contribution of epithelial-derived fibroblasts to bleomycin-induced lung fibrosis. Am J Respir Crit Care Med. 2009;180(7):657.

Wick P, Manser P, Limbach LK, Dettlaff-Weglikowska U, Krumeich F, Roth S, Stark WJ, Bruinink A. The degree and kind of agglomeration affect carbon nanotube cytotoxicity. Toxicol Lett. 2007;168(2):121.

Shvedova AA, Kisin ER, Porter D, Schulte P, Kagan VE, Fadeel B, Castranova V. Mechanisms of pulmonary toxicity and medical applications of carbon nanotubes: two faces of Janus? Pharmacol Ther. 2009;121(2):192.

Palomäki J, Välimäki E, Sund J, Vippola M, Clausen PA, Jensen KA, Savolainen K, Matikainen S, Alenius H. Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism. ACS Nano. 2011;5(9):6861.

Yilmaz M, Christofori G. EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009;28(1–2):15.

Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871.

Chakrabarti S, Patel KD. Matrix metalloproteinase-2 (MMP-2) and MMP-9 in pulmonary pathology. Exp Lung Res. 2005;31(6):599.

Guarino M, Tosoni A, Nebuloni M. Direct contribution of epithelium to organ fibrosis: epithelial-mesenchymal transition. Hum Pathol. 2009;40(10):1365.

Ronzani C, Spiegelhalter C, Vonesch JL, Lebeau L, Pons F. Lung deposition and toxicological responses evoked by multi-walled carbon nanotubes dispersed in a synthetic lung surfactant in the mouse. Arch Toxicol. 2012;86(1):137.

Chen T, Zang J, Wang H, Nie H, Wang X, Shen Z, Tang S, Yang J, Jia G. Water-soluble taurine-functionalized multi-walled carbon nanotubes induce less damage to mitochondria of RAW 264.7 cells. J Nanosci Nanotechnol. 2012;12(10):8008.

Wang X, Guo J, Chen T, Nie H, Wang H, Zang J, Cui X, Jia G. Multi-walled carbon nanotubes induce apoptosis via mitochondrial pathway and scavenger receptor. Toxicol In Vitro. 2012;26(6):799.

Zucchini-Pascal N, Peyre L, Rahmani R. Crosstalk between beta-catenin and snail in the induction of epithelial to mesenchymal transition in hepatocarcinoma: role of the ERK1/2 pathway. Int J Mol Sci. 2013;14(10):20768.

Nawshad A, Lagamba D, Polad A, Hay ED. Transforming growth factor-beta signaling during epithelial-mesenchymal transformation: implications for embryogenesis and tumor metastasis. Cells Tissues Organs. 2005;179(1–2):11.

Grosse Y, Loomis D, Guyton KZ, Lauby-Secretan B, Ghissassi FE, Bouvard V, Benbrahim-Tallaa L, Guha N, Scoccianti C, Mattock H, Straif K. Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes. Lancet Oncol. 2014;15:1427.

Vietti G, Ibouraadaten S, Palmai-Pallag M, Yakoub Y, Bailly C, Fenoglio I, Marbaix E, Lison D, van den Brule S. Towards predicting the lung fibrogenic activity of nanomaterials: experimental validation of an in vitro fibroblast proliferation assay. Part Fibre Toxicol. 2013;10:52.