Titanium nanoparticle inhalation induces renal fibrosis in mice via an oxidative stress upregulated transforming growth factor-β pathway

Chemical Research in Toxicology

Volumn 28, Issue 3, 2015, Pages 354-364

  Huang, Kuo Tong ^a,b   Wu, Cheng Tien ^a   Huang, Kuo How ^a   Lin, Wei Chou ^b   Chen, Chang Mu ^b   Guan, Siao Syun ^a,c   Chiang, Chih Kang ^a,b   Liu, Shing Hwa ^a,d  

^a NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^c INSTITUTE OF NUCLEAR ENERGY RESEARCH   (Taiwan)

^d CHINA MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

3 NITROTYROSINE; ACETYLCYSTEINE; COLLAGEN TYPE 1; HEME OXYGENASE 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INDUCIBLE NITRIC OXIDE SYNTHASE; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; TITANIUM DIOXIDE NANOPARTICLE; TRANSFORMING GROWTH FACTOR BETA; HIF1A PROTEIN, MOUSE; INTERLEUKIN 1BETA; MESSENGER RNA; METAL NANOPARTICLE; NOS2 PROTEIN, MOUSE; TITANIUM; TITANIUM DIOXIDE; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRUSH BORDER; CELL ORGANELLE; CONTROLLED STUDY; EXTRACELLULAR MATRIX; GRANULOCYTE; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; INHALATION; KIDNEY; KIDNEY FIBROSIS; LUNG PARENCHYMA; MOUSE; NONHUMAN; OXIDATIVE STRESS; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TRANSMISSION ELECTRON MICROSCOPY; UREA NITROGEN BLOOD LEVEL; ANIMAL; BIOSYNTHESIS; CELL LINE; CHEMICALLY INDUCED; DRUG EFFECTS; FIBROSIS; GENETICS; INHALATIONAL DRUG ADMINISTRATION; INSTITUTE FOR CANCER RESEARCH MOUSE; KIDNEY DISEASE; MALE; METABOLISM; PATHOLOGY;

ANIMALIA; MUS;

ADMINISTRATION, INHALATION; ANIMALS; CELL LINE; COLLAGEN TYPE I; FIBROSIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INTERLEUKIN-1BETA; KIDNEY; KIDNEY DISEASES; MALE; METAL NANOPARTICLES; MICE, INBRED ICR; NITRIC OXIDE SYNTHASE TYPE II; OXIDATIVE STRESS; RNA, MESSENGER; TITANIUM; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84924904522     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx500287f     Document Type: Article

References (76)

1. Hristozov, D., Zabeo, A., Foran, C. M., Critto, A., Marcomini, A., Isigonis, P., and Linkov, I. (2014) A weight of evidence approach for hazard screening of engineered nanomaterials Nanotoxicology 8, 72-87
2. Iavicoli, I., Leso, V., Fontana, L., and Bergamaschi, A. (2011) Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies Eur. Rev. Med. Pharmacol. Sci. 15, 481-508
3. Senzui, M., Tamura, T., Miura, K., Ikarashi, Y., Watanabe, Y., and Fujii, M. (2010) Study on penetration of titanium dioxide (TiO(2)) nanoparticles into intact and damaged skin in vitro J. Toxicol. Sci. 35, 107-113
4. Jaeger, A., Weiss, D. G., Jonas, L., and Kriehuber, R. (2012) Oxidative stress-induced cytotoxic and genotoxic effects of nano-sized titanium dioxide particles in human HaCaT keratinocytes Toxicology 296, 27-36
5. Eydner, M., Schaudien, D., Creutzenberg, O., Ernst, H., Hansen, T., Baumgartner, W., and Rittinghausen, S. (2012) Impacts after inhalation of nano- and fine-sized titanium dioxide particles: morphological changes, translocation within the rat lung, and evaluation of particle deposition using the relative deposition index Inhalation Toxicol. 24, 557-569
6. Scherbart, A. M., Langer, J., Bushmelev, A., van Berlo, D., Haberzettl, P., van Schooten, F. J., Schmidt, A. M., Rose, C. R., Schins, R. P., and Albrecht, C. (2011) Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms Part. Fibre Toxicol. 8, 1-19
7. Fabian, E., Landsiedel, R., Ma-Hock, L., Wiench, K., Wohlleben, W., and van Ravenzwaay, B. (2008) Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats Arch. Toxicol. 82, 151-157
8. Andujar, P., Lanone, S., Brochard, P., and Boczkowski, J. (2009) Respiratory effects of manufactured nanoparticles Rev. Mal. Respir. 26, 625-637
9. Chen, H. W., Su, S. F., Chien, C. T., Lin, W. H., Yu, S. L., Chou, C. C., Chen, J. J., and Yang, P. C. (2006) Titanium dioxide nanoparticles induce emphysema-like lung injury in mice FASEB J. 20, 2393-2395
10. Nurkiewicz, T. R., Porter, D. W., Hubbs, A. F., Stone, S., Chen, B. T., Frazer, D. G., Boegehold, M. A., and Castranova, V. (2009) Pulmonary nanoparticle exposure disrupts systemic microvascular nitric oxide signaling Toxicol. Sci. 110, 191-203
11. LeBlanc, A. J., Cumpston, J. L., Chen, B. T., Frazer, D., Castranova, V., and Nurkiewicz, T. R. (2009) Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles J. Toxicol. Environ. Health A 72, 1576-1584
12. Kermanizadeh, A., Gaiser, B. K., Hutchison, G. R., and Stone, V. (2012) An in vitro liver model - assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials Part. Fibre Toxicol. 9, 28
13. Fu, Y., Zhang, Y., Chang, X., Ma, S., Sui, J., Yin, L., Pu, Y., and Liang, G. (2014) Systemic immune effects of titanium dioxide nanoparticles after repeated intratracheal instillation in rat Int. J. Mol. Sci. 15, 6961-6973
14. Chen, J., Dong, X., Zhao, J., and Tang, G. (2009) In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection J. Appl. Toxicol. 29, 330-337
15. LAzou, B., Jorly, J., On, D., Sellier, E., Moisan, F., Fleury-Feith, J., Cambar, J., Brochard, P., and Ohayon-Courtes, C. (2008) In vitro effects of nanoparticles on renal cells Part. Fibre Toxicol. 5, 22
16. Wang, J., Zhou, G., Chen, C., Yu, H., Wang, T., Ma, Y., Jia, G., Gao, Y., Li, B., Sun, J., Li, Y., Jiao, F., Zhao, Y., and Chai, Z. (2007) Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration Toxicol. Lett. 168, 176-185
17. Gui, S., Zhang, Z., Zheng, L., Cui, Y., Liu, X., Li, N., Sang, X., Sun, Q., Gao, G., Cheng, Z., Cheng, J., Wang, L., Tang, M., and Hong, F. (2011) Molecular mechanism of kidney injury of mice caused by exposure to titanium dioxide nanoparticles J. Hazard. Mater. 195, 365-370
18. Gui, S., Sang, X., Zheng, L., Ze, Y., Zhao, X., Sheng, L., Sun, Q., Cheng, Z., Cheng, J., Hu, R., Wang, L., Hong, F., and Tang, M. (2013) Intragastric exposure to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by physiological and gene expression modifications Part. Fibre Toxicol. 10, 4
19. Gui, S., Li, B., Zhao, X., Sheng, L., Hong, J., Yu, X., Sang, X., Sun, Q., Ze, Y., Wang, L., and Hong, F. (2013) Renal injury and Nrf2 modulation in mouse kidney following chronic exposure to TiO(2) nanoparticles J. Agric. Food Chem. 61, 8959-8968
20. Ma, H., Brennan, A., and Diamond, S. A. (2012) Photocatalytic reactive oxygen species production and phototoxicity of titanium dioxide nanoparticles are dependent on the solar ultraviolet radiation spectrum Environ. Toxicol. Chem. 31, 2099-2107
21. Goven, D., Boutten, A., Lecon-Malas, V., Marchal-Somme, J., Soler, P., Boczkowski, J., and Bonay, M. (2010) Induction of heme oxygenase-1, biliverdin reductase and H-ferritin in lung macrophage in smokers with primary spontaneous pneumothorax: role of HIF-1alpha PLoS One 5, e10886
22. Semenza, G. L. (2009) Regulation of oxygen homeostasis by hypoxia-inducible factor 1 Physiology 24, 97-106
23. Higgins, D. F., Kimura, K., Bernhardt, W. M., Shrimanker, N., Akai, Y., Hohenstein, B., Saito, Y., Johnson, R. S., Kretzler, M., Cohen, C. D., Eckardt, K. U., Iwano, M., and Haase, V. H. (2007) Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition J. Clin. Invest. 117, 3810-3820
24. Haase, V. H. (2006) Hypoxia-inducible factors in the kidney Am. J. Physiol. Renal Physiol. 291, F271-F281
25. Eckardt, K. U., Bernhardt, W. M., Weidemann, A., Warnecke, C., Rosenberger, C., Wiesener, M. S., and Willam, C. (2005) Role of hypoxia in the pathogenesis of renal disease Kidney Int. Suppl S46-51
26. Pialoux, V., Mounier, R., Brown, A. D., Steinback, C. D., Rawling, J. M., and Poulin, M. J. (2009) Relationship between oxidative stress and HIF-1 alpha mRNA during sustained hypoxia in humans Free Radical Biol. Med. 46, 321-326
27. Zhou, J., Fandrey, J., Schumann, J., Tiegs, G., and Brune, B. (2003) NO and TNF-alpha released from activated macrophages stabilize HIF-1alpha in resting tubular LLC-PK1 cells Am. J. Physiol. Cell Physiol. 284, C439-C446
28. Kobayashi, H., Gilbert, V., Liu, Q., Kapitsinou, P. P., Unger, T. L., Rha, J., Rivella, S., Schlondorff, D., and Haase, V. H. (2012) Myeloid cell-derived hypoxia-inducible factor attenuates inflammation in unilateral ureteral obstruction-induced kidney injury J. Immunol. 188, 5106-5115
29. Sandau, K. B., Zhou, J., Kietzmann, T., and Brune, B. (2001) Regulation of the hypoxia-inducible factor 1alpha by the inflammatory mediators nitric oxide and tumor necrosis factor-alpha in contrast to desferroxamine and phenylarsine oxide J. Biol. Chem. 276, 39805-39811
30. Tanaka, T. and Nangaku, M. (2010) The role of hypoxia, increased oxygen consumption, and hypoxia-inducible factor-1 alpha in progression of chronic kidney disease Curr. Opin. Nephrol. Hypertens. 19, 43-50
31. Higgins, D. F., Biju, M. P., Akai, Y., Wutz, A., Johnson, R. S., and Haase, V. H. (2004) Hypoxic induction of Ctgf is directly mediated by Hif-1 Am. J. Physiol. Renal Physiol. 287, F1223-F1232
32. Basu, R. K., Hubchak, S., Hayashida, T., Runyan, C. E., Schumacker, P. T., and Schnaper, H. W. (2011) Interdependence of HIF-1alpha and TGF-beta/Smad3 signaling in normoxic and hypoxic renal epithelial cell collagen expression Am. J. Physiol. Renal Physiol. 300, F898-F905
33. Liang, G., Pu, Y., Yin, L., Liu, R., Ye, B., Su, Y., and Li, Y. (2009) Influence of different sizes of titanium dioxide nanoparticles on hepatic and renal functions in rats with correlation to oxidative stress J. Toxicol. Environ. Health A 72, 740-745
34. Rayamajhi, M., Redente, E. F., Condon, T. V., Gonzalez-Juarrero, M., Riches, D. W., and Lenz, L. L. (2011) Non-surgical intratracheal instillation of mice with analysis of lungs and lung draining lymph nodes by flow cytometry J. Vis. Exp. 2702
35. Sturrock, A. M., Hunter, E., Milton, J. A., and Trueman, C. N. (2013) Analysis methods and reference concentrations of 12 minor and trace elements in fish blood plasma J. Trace Elem. Med. Biol. 27, 273-285
36. Asanuma, H., Vanderbrink, B. A., Campbell, M. T., Hile, K. L., Zhang, H., Meldrum, D. R., and Meldrum, K. K. (2011) Arterially delivered mesenchymal stem cells prevent obstruction-induced renal fibrosis J. Surg. Res. 168, e51-e59
37. Wu, C. T., Weng, T. I., Chen, L. P., Chiang, C. K., and Liu, S. H. (2012) Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury Toxicol. Appl. Pharmacol. 266, 167-175
38. Pulskens, W. P., Rampanelli, E., Teske, G. J., Butter, L. M., Claessen, N., Luirink, I. K., van der Poll, T., Florquin, S., and Leemans, J. C. (2010) TLR4 promotes fibrosis but attenuates tubular damage in progressive renal injury J. Am. Soc. Nephrol. 21, 1299-1308
39. Roberts, I. S., Cook, H. T., Troyanov, S., Alpers, C. E., Amore, A., Barratt, J., Berthoux, F., Bonsib, S., Bruijn, J. A., Cattran, D. C., Coppo, R., DAgati, V., DAmico, G., Emancipator, S., Emma, F., Feehally, J., Ferrario, F., Fervenza, F. C., Florquin, S., Fogo, A., Geddes, C. C., Groene, H. J., Haas, M., Herzenberg, A. M., Hill, P. A., Hogg, R. J., Hsu, S. I., Jennette, J. C., Joh, K., Julian, B. A., Kawamura, T., Lai, F. M., Li, L. S., Li, P. K., Liu, Z. H., Mackinnon, B., Mezzano, S., Schena, F. P., Tomino, Y., Walker, P. D., Wang, H., Weening, J. J., Yoshikawa, N., and Zhang, H. (2009) The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility Kidney Int. 76, 546-556
40. Brun, E., Barreau, F., Veronesi, G., Fayard, B., Sorieul, S., Chaneac, C., Carapito, C., Rabilloud, T., Mabondzo, A., Herlin-Boime, N., and Carriere, M. (2014) Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia Part. Fibre Toxicol. 11, 13
41. Jugan, M. L., Barillet, S., Simon-Deckers, A., Herlin-Boime, N., Sauvaigo, S., Douki, T., and Carriere, M. (2012) Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells Nanotoxicology 6, 501-513
42. Eruslanov, E. and Kusmartsev, S. (2010) Identification of ROS using oxidized DCFDA and flow-cytometry Methods Mol. Biol. 594, 57-72
43. Wu, C. T., Sheu, M. L., Tsai, K. S., Chiang, C. K., and Liu, S. H. (2011) Salubrinal, an eIF2alpha dephosphorylation inhibitor, enhances cisplatin-induced oxidative stress and nephrotoxicity in a mouse model Free Radical Biol. Med. 51, 671-680
44. Ozer, J. S., Dieterle, F., Troth, S., Perentes, E., Cordier, A., Verdes, P., Staedtler, F., Mahl, A., Grenet, O., Roth, D. R., Wahl, D., Legay, F., Holder, D., Erdos, Z., Vlasakova, K., Jin, H., Yu, Y., Muniappa, N., Forest, T., Clouse, H. K., Reynolds, S., Bailey, W. J., Thudium, D. T., Topper, M. J., Skopek, T. R., Sina, J. F., Glaab, W. E., Vonderscher, J., Maurer, G., Chibout, S. D., Sistare, F. D., and Gerhold, D. L. (2010) A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function Nat. Biotechnol. 28, 486-494
45. Long, T. C., Tajuba, J., Sama, P., Saleh, N., Swartz, C., Parker, J., Hester, S., Lowry, G. V., and Veronesi, B. (2007) Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro Environ. Health Perspect. 115, 1631-1637
46. Gurr, J. R., Wang, A. S., Chen, C. H., and Jan, K. Y. (2005) Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells Toxicology 213, 66-73
47. Nurkiewicz, T. R., Porter, D. W., Barger, M., Millecchia, L., Rao, K. M., Marvar, P. J., Hubbs, A. F., Castranova, V., and Boegehold, M. A. (2006) Systemic microvascular dysfunction and inflammation after pulmonary particulate matter exposure Environ. Health Perspect. 114, 412-419
48. Kitada, M., Kume, S., Imaizumi, N., and Koya, D. (2011) Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of Mn-SOD dysfunction in AMPK/SIRT1-independent pathway Diabetes 60, 634-643
49. Yang, Z. Z., Zhang, A. Y., Yi, F. X., Li, P. L., and Zou, A. P. (2003) Redox regulation of HIF-1alpha levels and HO-1 expression in renal medullary interstitial cells Am. J. Physiol. Renal Physiol. 284, F1207-1215
50. Haase, V. H. (2009) Pathophysiological Consequences of HIF Activation: HIF as a modulator of fibrosis Ann. N.Y. Acad. Sci. 1177, 57-65
51. Yeligar, S. M., Machida, K., and Kalra, V. K. (2010) Ethanol-induced HO-1 and NQO1 are differentially regulated by HIF-1alpha and Nrf2 to attenuate inflammatory cytokine expression J. Biol. Chem. 285, 35359-35373
52. Halasi, M., Wang, M., Chavan, T. S., Gaponenko, V., Hay, N., and Gartel, A. L. (2013) ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors Biochem. J. 454, 201-208
53. Corbett, J. A. and McDaniel, M. L. (1996) The Use of Aminoguanidine, a selective iNOS inhibitor, to evaluate the role of nitric oxide in the development of autoimmune diabetes Methods 10, 21-30
54. Morishige, T., Yoshioka, Y., Tanabe, A., Yao, X., Tsunoda, S., Tsutsumi, Y., Mukai, Y., Okada, N., and Nakagawa, S. (2010) Titanium dioxide induces different levels of IL-1beta production dependent on its particle characteristics through caspase-1 activation mediated by reactive oxygen species and cathepsin B Biochem. Biophys. Res. Commun. 392, 160-165
55. Park, E. J., Yoon, J., Choi, K., Yi, J., and Park, K. (2009) Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation Toxicology 260, 37-46
56. Wang, J., Liu, Y., Jiao, F., Lao, F., Li, W., Gu, Y., Li, Y., Ge, C., Zhou, G., Li, B., Zhao, Y., Chai, Z., and Chen, C. (2008) Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO(2) nanoparticles Toxicology 254, 82-90
57. Sayes, C. M., Wahi, R., Kurian, P. A., Liu, Y., West, J. L., Ausman, K. D., Warheit, D. B., and Colvin, V. L. (2006) Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells Toxicol. Sci. 92, 174-185
58. Grassian, V. H., OShaughnessy, P. T., Adamcakova-Dodd, A., Pettibone, J. M., and Thorne, P. S. (2007) Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm Environ. Health Perspect. 115, 397-402
59. Scown, T. M., van Aerle, R., Johnston, B. D., Cumberland, S., Lead, J. R., Owen, R., and Tyler, C. R. (2009) High doses of intravenously administered titanium dioxide nanoparticles accumulate in the kidneys of rainbow trout but with no observable impairment of renal function Toxicol. Sci. 109, 372-380
60. Lee, K. P., Trochimowicz, H. J., and Reinhardt, C. F. (1985) Pulmonary response of rats exposed to titanium dioxide (TiO2) by inhalation for two years Toxicol. Appl. Pharmacol. 79, 179-192
61. Afaq, F., Abidi, P., Matin, R., and Rahman, Q. (1998) Cytotoxicity, pro-oxidant effects and antioxidant depletion in rat lung alveolar macrophages exposed to ultrafine titanium dioxide J. Appl. Toxicol. 18, 307-312
62. Oberdorster, G., Finkelstein, J. N., Johnston, C., Gelein, R., Cox, C., Baggs, R., and Elder, A. C. (2000) Acute pulmonary effects of ultrafine particles in rats and mice Res. Rep. Health Eff. Inst. 5-74 discussion 75-86.
63. Oberdorster, G., Oberdorster, E., and Oberdorster, J. (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles Environ. Health Perspect. 113, 823-839
64. Li, Y., Li, J., Yin, J., Li, W., Kang, C., Huang, Q., and Li, Q. (2010) Systematic influence induced by 3 nm titanium dioxide following intratracheal instillation of mice J. Nanosci. Nanotechnol. 10, 8544-8549
65. Sager, T. M., Kommineni, C., and Castranova, V. (2008) Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area Part. Fibre Toxicol. 5, 17
66. Oberdorster, G., Ferin, J., and Lehnert, B. E. (1994) Correlation between particle size, in vivo particle persistence, and lung injury Environ. Health Perspect. 102 (Suppl 5) 173-179
67. Muhlfeld, C., Geiser, M., Kapp, N., Gehr, P., and Rothen-Rutishauser, B. (2007) Re-evaluation of pulmonary titanium dioxide nanoparticle distribution using the relative deposition index: Evidence for clearance through microvasculature Part. Fibre Toxicol. 4, 7
68. Shi, H., Magaye, R., Castranova, V., and Zhao, J. (2013) Titanium dioxide nanoparticles: a review of current toxicological data Part. Fibre Toxicol. 10, 15
69. Wang, J., Chen, C., Liu, Y., Jiao, F., Li, W., Lao, F., Li, Y., Li, B., Ge, C., Zhou, G., Gao, Y., Zhao, Y., and Chai, Z. (2008) Potential neurological lesion after nasal instillation of TiO(2) nanoparticles in the anatase and rutile crystal phases Toxicol. Lett. 183, 72-80
70. Yazdi, A. S., Guarda, G., Riteau, N., Drexler, S. K., Tardivel, A., Couillin, I., and Tschopp, J. (2010) Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1alpha and IL-1beta Proc. Natl. Acad. Sci. U.S.A. 107, 19449-19454
71. Bermudez, E., Mangum, J. B., Asgharian, B., Wong, B. A., Reverdy, E. E., Janszen, D. B., Hext, P. M., Warheit, D. B., and Everitt, J. I. (2002) Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles Toxicol. Sci. 70, 86-97
72. Hervouet, E., Cizkova, A., Demont, J., Vojtiskova, A., Pecina, P., Franssen-van Hal, N. L., Keijer, J., Simonnet, H., Ivanek, R., Kmoch, S., Godinot, C., and Houstek, J. (2008) HIF and reactive oxygen species regulate oxidative phosphorylation in cancer Carcinogenesis 29, 1528-1537
73. Czibik, G., Sagave, J., Martinov, V., Ishaq, B., Sohl, M., Sefland, I., Carlsen, H., Farnebo, F., Blomhoff, R., and Valen, G. (2009) Cardioprotection by hypoxia-inducible factor 1 alpha transfection in skeletal muscle is dependent on haem oxygenase activity in mice Cardiovasc. Res. 82, 107-114
74. Sikorski, E. M., Hock, T., Hill-Kapturczak, N., and Agarwal, A. (2004) The story so far: Molecular regulation of the heme oxygenase-1 gene in renal injury Am. J. Physiol. Renal. Physiol. 286, F425-441
75. Bolisetty, S., Traylor, A. M., Kim, J., Joseph, R., Ricart, K., Landar, A., and Agarwal, A. (2010) Heme oxygenase-1 inhibits renal tubular macroautophagy in acute kidney injury J. Am. Soc. Nephrol. 21, 1702-1712
76. Hill-Kapturczak, N., Truong, L., Thamilselvan, V., Visner, G. A., Nick, H. S., and Agarwal, A. (2000) Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor-beta in human renal epithelial cells J. Biol. Chem. 275, 40904-40909