NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury
Open accessAbstract
Members of the NADPH oxidase (NOX) family of enzymes, which catalyze the reduction of O(2) to reactive oxygen species, have increased in number during eukaryotic evolution. Seven isoforms of the NOX gene family have been identified in mammals; however, specific roles of NOX enzymes in mammalian physiology and pathophysiology have not been fully elucidated. The best established physiological role of NOX enzymes is in host defense against pathogen invasion in diverse species, including plants. The prototypical member of this family, NOX-2 (gp91(phox)), is expressed in phagocytic cells and mediates microbicidal activities. Here we report a role for the NOX4 isoform in tissue repair functions of myofibroblasts and fibrogenesis. Transforming growth factor-beta1 (TGF-beta1) induces NOX-4 expression in lung mesenchymal cells via SMAD-3, a receptor-regulated protein that modulates gene transcription. NOX-4-dependent generation of hydrogen peroxide (H(2)O(2)) is required for TGF-beta1-induced myofibroblast differentiation, extracellular matrix (ECM) production and contractility. NOX-4 is upregulated in lungs of mice subjected to noninfectious injury and in cases of human idiopathic pulmonary fibrosis (IPF). Genetic or pharmacologic targeting of NOX-4 abrogates fibrogenesis in two murine models of lung injury. These studies support a function for NOX4 in tissue fibrogenesis and provide proof of concept for therapeutic targeting of NOX-4 in recalcitrant fibrotic disorders.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Although NOX4 activity has been shown to reduce fibrosis in atherosclerosis, it can also promote fibrosis, particularly in the lung, but also in kidney and other tissues.
“In a final note, it should be also considered that although NOX4 activity has been shown to reduce fibrosis in atherosclerosis (230), it can also promote fibrosis, particularly in the lung, but also in kidney and other tissues (110, 201, 416, 596, 820).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [416]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
The large-conductance Ca2+-activated K+ channel is essential for innate immunity
Ahluwalia, J., Tinker, A., Clapp, L. H., Duchen, M. R., Abramov, A. Y., Pope, S. A. S., Nobles, M., & Segal, A. W. (2004) · Nature · doi:10.1038/nature02356 · Cited by 206 · see citing works
RetractedThe NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · see citing works
Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290 · see citing works
NOX enzymes and the biology of reactive oxygen
Lambeth, J. D. (2004) · Nature Reviews Immunology · doi:10.1038/nri1312 · Cited by 3,125 · see citing works
H2O2 from the oxidative burst orchestrates the plant hypersensitive disease resistance response
Levine, A., Tenhaken, R., Dixon, R. A., & Lamb, C. J. (1994) · Cell · doi:10.1016/0092-8674(94)90544-4 · Cited by 2,767 · see citing works
Desmoulière, A., Geinoz, A., Gabbiani, F., & Gabbiani, G. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.1.103 · Cited by 2,226 · see citing works
Hinz, B., Phan, S. H., Thannickal, V. J., Galli, A., Bochaton-Piallat, M.-L., & Gabbiani, G. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070112 · Cited by 2,068 · see citing works
Self-citationIncidence and Prevalence of Idiopathic Pulmonary Fibrosis
Raghu, G., Weycker, D., Edelsberg, J., Bradford, W. Z., & Oster, G. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200602-163oc · Cited by 1,310 · see citing works
Quie, P. G., White, J. G., Holmes, B. M., & Good, R. A. (1967) · Journal of Clinical Investigation · doi:10.1172/jci105568 · Cited by 906 · see citing works
Serini, G., Bochaton-Piallat, M.-L., Ropraz, P., Geinoz, A., Borsi, L., Zardi, L., & Gabbiani, G. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.3.873 · Cited by 847 · see citing works
Mechanisms of Pulmonary Fibrosis
Thannickal, V. J., Toews, G. B., White, E. S., Lynch, J. P., & Martínez, F. J. (2004) · Annual Review of Medicine · doi:10.1146/annurev.med.55.091902.103810 · Cited by 806 · see citing works
Self-citationCucoranu, I., Clempus, R., Dikalova, A., Phelan, P. J., Ariyan, S., Dikalov, S., & Sorescu, D. (2005) · Circulation Research · doi:10.1161/01.res.0000187457.24338.3d · Cited by 786 · see citing works
Sumimoto, H. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06488.x · Cited by 718 · see citing works
Nox enzymes, ROS, and chronic disease: An example of antagonistic pleiotropy
Lambeth, J. D. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.03.027 · Cited by 677 · see citing works
Hinz, B., Mastrangelo, D., Iselin, C. E., Chaponnier, C., & Gabbiani, G. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61776-2 · Cited by 638 · see citing works
Thannickal, V. J., Lee, D. Y., White, E. S., Cui, Z., Larios, J. M., Chacon, R., Horowitz, J. C., Day, R. M., & Thomas, P. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208544200 · Cited by 606 · see citing works
Self-citationZhang, K., Rekhter, M. D., Gordon, D., & Phan, S. H. (1994) · PubMed Central · Cited by 477 · see citing works
The Nox Family of NAD(P)H Oxidases: Host Defense and Beyond
Geiszt, M., & Leto, T. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r400024200 · Cited by 452 · see citing works
Thannickal, V. J., & Fanburg, B. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.51.30334 · Cited by 424 · see citing works
Self-citationSmad3 Null Mice Develop Airspace Enlargement and Are Resistant to TGF-β-Mediated Pulmonary Fibrosis
Bonniaud, P., Kolb, M. R. J., Galt, T., Robertson, J. V., Robbins, C. S., Stämpfli, M. R., Lavery, C., Margetts, P. J., Roberts, A. B., & Gauldie, J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.2099 · Cited by 383 · see citing works
Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox/Duox) family of enzymes
Kawahara, T., Quinn, M. T., & Lambeth, J. D. (2007) · BMC Evolutionary Biology · doi:10.1186/1471-2148-7-109 · Cited by 336 · see citing works
NOX family NADPH oxidases: Not just in mammals
Bedard, K., Lardy, B., & KRAUSE, K. (2007) · Biochimie · doi:10.1016/j.biochi.2007.01.012 · Cited by 321 · see citing works
Waghray, M., Cui, Z., Horowitz, J. C., Subramanian, I. M., Martínez, F. J., Toews, G. B., & Thannickal, V. J. (2005) · The FASEB Journal · doi:10.1096/fj.04-2882fje · Cited by 269 · see citing works
Self-citationBleomycin-induced pulmonary fibrosis in fibrinogen-null mice
Hattori, N., Degen, J. L., Sisson, T. H., Liu, H., Moore, B. B., Pandrangi, R. G., Simon, R. H., & Drew, A. F. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10531 · Cited by 264 · see citing works
Horowitz, J. C., Lee, D. Y., Waghray, M., Keshamouni, V. G., Thomas, P. E., Zhang, H., Cui, Z., & Thannickal, V. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306248200 · Cited by 239 · see citing works
Self-citationVittal, R., Horowitz, J. C., Moore, B. B., Zhang, H., Martínez, F. J., Toews, G. B., Standiford, T. J., & Thannickal, V. J. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62260-2 · Cited by 126 · see citing works
Self-citationOxygen in the evolution of complex life and the price we pay
Thannickal, V. J. (2009) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2008-0360ps · Cited by 116 · see citing works
Self-citationThrall, R. S., Barton, R. W., D'Amato, D. A., & Sulavik, S. B. (1982) · PubMed · doi:10.1164/arrd.1982.126.3.488 · Cited by 97 · see citing works
A novel model for human interstitial lung disease: Hapten‐driven lung fibrosis in rodents
Roberts, S., Howie, S., Wallace, W. A., Brown, D. M., Lamb, D., Ramage, E., & Donaldson, K. (1995) · The Journal of Pathology · doi:10.1002/path.1711760313 · Cited by 47 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nathan, C., & Ding, A. (2010) · Cell · doi:10.1016/j.cell.2010.02.029 · Cited by 2,183 · see citing works
Integrating mechanisms of pulmonary fibrosis
Wynn, T. A. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110551 · Cited by 1,282 · see citing works
Recent Developments in Myofibroblast Biology
Hinz, B., Phan, S. H., Thannickal, V. J., Prunotto, M., Desmoulière, A., Varga, J., De Wever, O., Mareel, M., & Gabbiani, G. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.02.004 · Cited by 1,193 · see citing works
Self-citationmiR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis
Liu, G., Friggeri, A., Yang, Y., Milosevic, J., Ding, Q., Thannickal, V. J., Kaminski, N., & Abraham, E. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100035 · Cited by 935 · see citing works
Self-citationTGF-β signaling in health and disease
Massagué, J., & Sheppard, D. (2023) · Cell · doi:10.1016/j.cell.2023.07.036 · Cited by 890 · see citing works
TGF-β1 Signaling and Tissue Fibrosis
Kim, K. K., Sheppard, D., & Chapman, H. A. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022293 · Cited by 800 · see citing works
Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance
Hecker, L., Logsdon, N. J., Kurundkar, D., Kurundkar, A., Bernard, K., Hock, T., Meldrum, E., Sanders, Y. Y., & Thannickal, V. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008182 · Cited by 686 · see citing works
Self-citationReciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis
Liu, R.-M., & Desai, L. P. (2015) · Redox Biology · doi:10.1016/j.redox.2015.09.009 · Cited by 684 · see citing works
The Impact of TGF-β on Lung Fibrosis: From Targeting to Biomarkers
Fernandez, I. E., & Eickelberg, O. (2012) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201203-023aw · Cited by 682 · see citing works
Therapy for Fibrotic Diseases: Nearing the Starting Line
Friedman, S. L., Sheppard, D., Duffield, J. S., & Violette, S. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004700 · Cited by 655 · see citing works
Host Responses in Tissue Repair and Fibrosis
Duffield, J. S., Lupher, M., Thannickal, V. J., & Wynn, T. A. (2012) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163930 · Cited by 624 · see citing works
Self-citationPulmonary fibrosis: patterns and perpetrators
Noble, P. W., Barkauskas, C. E., & Jiang, D. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60323 · Cited by 595 · see citing works
Metformin reverses established lung fibrosis in a bleomycin model
Rangarajan, S., Bone, N. B., Zmijewska, A. A., Jiang, S., Park, D. W., Bernard, K. F., Locy, M. L., Ravi, S., Deshane, J. S., Mannon, R. B., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0087-6 · Cited by 565 · see citing works
Self-citationSources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
Oxidative stress and pulmonary fibrosis
Cheresh, P., Kim, S.-J., Tulasiram, S., & Kamp, D. W. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.11.021 · Cited by 527 · see citing works
Evolution of nadph oxidase inhibitors: Selectivity and mechanisms for target engagement
Altenhöfer, S., Radermacher, K. A., Kleikers, P. W. M., Wingler, K., & Schmidt, H. H. H. W. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5814 · Cited by 521 · see citing works
Nox enzymes and new thinking on reactive oxygen: A double-edged sword revisited
Lambeth, J. D., & Neish, A. S. (2014) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104651 · Cited by 495 · see citing works
Oxidative stress and glutathione in TGF-β-mediated fibrogenesis
Liu, R.-M., & Pravia, K. A. G. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.09.026 · Cited by 468 · see citing works
Antifibrotic activities of pirfenidone in animal models
Schaefer, C. J., Ruhrmund, D. W., Pan, L., Seiwert, S. D., & Kossen, K. (2011) · European Respiratory Review · doi:10.1183/09059180.00001111 · Cited by 454 · see citing works
Gibb, A., Lazaropoulos, M. P., & Elrod, J. W. (2020) · Circulation Research · doi:10.1161/circresaha.120.316958 · Cited by 443 · see citing works
New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis
Fernandez, I. E., & Eickelberg, O. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61144-1 · Cited by 434 · see citing works
Myofibroblast differentiation during fibrosis: role of NAD(P)H oxidases
Barnes, J. L., & Gorin, Y. C. (2011) · Kidney International · doi:10.1038/ki.2010.516 · Cited by 431 · see citing works
Macrophage Akt1 Kinase-Mediated Mitophagy Modulates Apoptosis Resistance and Pulmonary Fibrosis
Larson-Casey, J. L., Deshane, J. S., Ryan, A. J., Thannickal, V. J., & Carter, A. B. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.001 · Cited by 428 · see citing works
Self-citationHough, K. P., Curtiss, M. L., Blain, T. J., Liu, R.-M., Trevor, J., Deshane, J. S., & Thannickal, V. J. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00191 · Cited by 432 · see citing works
Self-citationThe Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders
Vona, R., Pallotta, L., Cappelletti, M., Severi, C., & Matarrese, P. (2021) · Antioxidants · doi:10.3390/antiox10020201 · Cited by 431 · see citing works
Molecular and cellular mechanisms of pulmonary fibrosis
Todd, N. W., Luzina, I. G., & Atamas, S. P. (2012) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-5-11 · Cited by 418 · see citing works
Redox homeostasis: The Golden Mean of healthy living
Ursini, F., Maiorino, M., & Forman, H. J. (2016) · Redox Biology · doi:10.1016/j.redox.2016.01.010 · Cited by 418 · see citing works
Evidence for a stromal-epithelial “lactate shuttle” in human tumors
Whitaker‐Menezes, D., Martinez‐Outschoorn, U., Lin, Z., Ertel, A., Flomenberg, N., Witkiewicz, A. K., Birbe, R., Howell, A., Pavlides, S., Gândara, R., et al. (2011) · Cell Cycle · doi:10.4161/cc.10.11.15659 · Cited by 413 · see citing works
Sedeek, M., Callera, G., Montezano, A., Gutsol, A., Heitz, F., Szyndralewiez, C., Page, P., Kennedy, C. R. J., Burns, K. D., Touyz, R. M., et al. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00028.2010 · Cited by 396 · see citing works
The NOX toolbox: validating the role of NADPH oxidases in physiology and disease
Altenhöfer, S., Kleikers, P. W. M., Radermacher, K. A., Scheurer, P., Rob Hermans, J. J., Schiffers, P., Ho, H., Wingler, K., & Schmidt, H. H. H. W. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1010-9 · Cited by 371 · see citing works
Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-β Signaling
Jain, M., Rivera, S., Monclus, E. A., Synenki, L., Zirk, A., Eisenbart, J. D., Feghali‐Bostwick, C. A., Mutlu, G. M., Budinger, G. R. S., & Chandel, N. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.431973 · Cited by 385 · see citing works
ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration
Feng, C., Yang, M., Lan, M., Liu, C., Zhang, Y., Huang, B., Liu, H., & Zhou, Y. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/5601593 · Cited by 384 · see citing works
Peripheral blood proteins predict mortality in idiopathic pulmonary fibrosis
Richards, T. J., Kaminski, N., Baribaud, F., Flavin, S., Brodmerkel, C., Horowitz, D., Li, K., Choi, J., Vuga, L. J., Lindell, K. O., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201101-0058oc · Cited by 381 · see citing works
Understanding fibrosis in systemic sclerosis: shifting paradigms, emerging opportunities
Bhattacharyya, S., Wei, J., & Varga, J. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.149 · Cited by 381 · see citing works
TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer
Caja, L., Dituri, F., Mancarella, S., Caballero‐Díaz, D., Moustakas, A., Giannelli, G., & Fabregat, I. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051294 · Cited by 353 · see citing works
Meiners, S., Eickelberg, O., & Königshoff, M. (2015) · European Respiratory Journal · doi:10.1183/09031936.00186914 · Cited by 340 · see citing works
Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis
Fabregat, I., & Caballero‐Díaz, D. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00357 · Cited by 352 · see citing works
Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis
Phan, T. H. G., Paliogiannis, P., Nasrallah, G. K., Giordo, R., Eid, A. H., Fois, A. G., Zinellu, A., Mangoni, A. A., & Pintus, G. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03693-7 · Cited by 355 · see citing works
Rice, L. M., Padilla, C. M., McLaughlin, S. R., Mathes, A., Ziemek, J., Goummih, S., Nakerakanti, S., York, M., Farina, G., Whitfield, M. L., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77958 · Cited by 351 · see citing works
Aoyama, T., Paik, Y.-H., Watanabe, S., Laleu, B., Gaggini, F., Fioraso-Cartier, L., Molango, S., Heitz, F., Merlot, C., Szyndralewiez, C., et al. (2012) · Hepatology · doi:10.1002/hep.25938 · Cited by 336 · see citing works
Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis
Palumbo‐Zerr, K., Zerr, P., Distler, A., Fliehr, J., Mancuso, R., Huang, J., Mielenz, D., Tomčík, M., Fürnrohr, B. G., Scholtysek, C., et al. (2015) · Nature Medicine · doi:10.1038/nm.3777 · Cited by 344 · see citing works
Amara, N., Goven, D., Prost, F., Muloway, R., Crestani, B., & Boczkowski, J. (2010) · Thorax · doi:10.1136/thx.2009.113456 · Cited by 335 · see citing works
Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries
Bezerra, F. S., Lanzetti, M., Nesi, R. T., Nagato, A. C., Silva, C. P. E., Kennedy-Feitosa, E., Melo, A. C., Cattani‐Cavalieri, I., Pôrto, L. C., & Valença, S. S. (2023) · Antioxidants · doi:10.3390/antiox12030548 · Cited by 353 · see citing works
Morry, J., Ngamcherdtrakul, W., & Yantasee, W. (2016) · Redox Biology · doi:10.1016/j.redox.2016.12.011 · Cited by 333 · see citing works
TGF-β signaling in tissue fibrosis: Redox controls, target genes and therapeutic opportunities
Samarakoon, R., Overstreet, J. M., & Higgins, P. J. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.10.003 · Cited by 333 · see citing works
Molecular mechanisms of oxidative stress in asthma
Michaeloudes, C., Abubakar-Waziri, H., Lakhdar, R., Raby, K., Dixey, P., Adcock, I. M., Mumby, S. E., Bhavsar, P. K., & Chung, K. F. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.101026 · Cited by 332 · see citing works
The myofibroblast, a key cell in normal and pathological tissue repair
Darby, I. A., Zakuan, N., Billet, F., & Desmoulière, A. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2110-0 · Cited by 328 · see citing works
The role of myofibroblasts in wound healing
Hinz, B. (2016) · Current Research in Translational Medicine · doi:10.1016/j.retram.2016.09.003 · Cited by 328 · see citing works
Milara, J., Peiró, T., Serrano, A., & Cortijo, J. (2013) · Thorax · doi:10.1136/thoraxjnl-2012-201761 · Cited by 324 · see citing works
Mechanisms of ultrafine particle-induced respiratory health effects
Leikauf, G. D., Kim, S., & Jang, A. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0394-0 · Cited by 323 · see citing works
Reactive oxygen species and fibrosis: further evidence of a significant liaison
Richter, K., & Kietzmann, T. (2016) · Cell and Tissue Research · doi:10.1007/s00441-016-2445-3 · Cited by 322 · see citing works
Yao, Y., Zhang, H., Wang, Z., Ding, J., Wang, S., Huang, B., Ke, S., & Gao, C. (2019) · Journal of Materials Chemistry B · doi:10.1039/c9tb00847k · Cited by 319 · see citing works
MicroRNAs in idiopathic pulmonary fibrosis
Pandit, K. V., Milošević, J., & Kaminski, N. (2011) · Translational research · doi:10.1016/j.trsl.2011.01.012 · Cited by 310 · see citing works
Egea, J., Fabregat, I., Frapart, Y., Ghezzi, P., Görlach, A., Kietzmann, T., Kubaichuk, K. I., Knaus, U. G., López, M. G., González, G. O., et al. (2017) · Redox Biology · doi:10.1016/j.redox.2017.05.007 · Cited by 311 · see citing works
A key role for nox4 in epithelial cell death during development of lung fibrosis
Carnesecchi, S., Deffert, C., Donati, Y., Basset, O., Hinz, B., Preynat-Seauve, O., Guichard, C., Arbiser, J. L., Banfi, B., Pache, J.-C., et al. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3829 · Cited by 290 · see citing works
Moon, J.-S., Nakahira, K., Chung, K.-P., DeNicola, G. M., Koo, M. J., Pabón, M. A., Rooney, K. T., Yoon, J.-H., Ryter, S. W., Stout-Delgado, H., et al. (2016) · Nature Medicine · doi:10.1038/nm.4153 · Cited by 291 · see citing works
RetractedCao, Z., Lis, R., Ginsberg, M., Chavez, D., Shido, K., Rabbany, S., Fong, G., Sakmar, T., Rafii, S., & Ding, B. (2016) · Nature Medicine · doi:10.1038/nm.4035 · Cited by 253 · see citing works
Fibrosis of two: Epithelial cell-fibroblast interactions in pulmonary fibrosis
Sakai, N., & Tager, A. M. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.03.001 · Cited by 286 · see citing works
ROS in gastrointestinal inflammation: Rescue Or Sabotage?
Aviello, G., & Knaus, U. G. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13428 · Cited by 282 · see citing works
Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases
Piera-Velázquez, S., Mendoza, F. A., & Jiménez, S. A. (2016) · Journal of Clinical Medicine · doi:10.3390/jcm5040045 · Cited by 276 · see citing works
NADPH oxidase-dependent redox signaling in TGF-β-mediated fibrotic responses
Jiang, F., Liu, G., Dusting, G. J., & Chan, E. C. (2014) · Redox Biology · doi:10.1016/j.redox.2014.01.012 · Cited by 270 · see citing works
NADPH oxidases in cardiovascular disease
Brandes, R. P., Weißmann, N., & Schröder, K. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.04.030 · Cited by 266 · see citing works
Oxidative Stress in Pulmonary Fibrosis
Otoupalova, E., Smith, S., Cheng, G., & Thannickal, V. J. (2020) · Comprehensive physiology · doi:10.1002/cphy.c190017 · Cited by 309 · see citing works
Self-citationJiang, J. X., Chen, X., Serizawa, N., Szyndralewiez, C., Page, P., Schröder, K., Brandes, R. P., Devaraj, S., & Török, N. J. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.05.007 · Cited by 251 · see citing works
Strategies for treating idiopathic pulmonary fibrosis
du Bois, R. M. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd2958 · Cited by 246 · see citing works
Ghouleh, I. A., Khoo, N. K. H., Knaus, U. G., Griendling, K. K., Touyz, R. M., Thannickal, V. J., Barchowsky, A., Nauseef, W. M., Kelley, E. E., Bauer, P. M., et al. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.06.011 · Cited by 249 · see citing works
Self-citationFibrosis: ultimate and proximate causes
Thannickal, V. J., Zhou, Y., Gaggar, A., & Duncan, S. R. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74368 · Cited by 241 · see citing works
Self-citationLaleu, B., Gaggini, F., Orchard, M., Fioraso-Cartier, L., Cagnon, L., Houngninou-Molango, S., Gradia, A., Duboux, G., Merlot, C., Heitz, F., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100773e · Cited by 243 · see citing works
Redox-fibrosis: Impact of TGFβ1 on ROS generators, mediators and functional consequences
Richter, K., Konzack, A., Pihlajaniemi, T. A., Heljäsvaara, R., & Kietzmann, T. (2015) · Redox Biology · doi:10.1016/j.redox.2015.08.015 · Cited by 240 · see citing works
NADPH oxidase 4 is an oncoprotein localized to mitochondria
Graham, K., Kulawiec, M., Owens, K. M., Li, X., Desouki, M. M., Chandra, D., & Singh, K. K. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.10.3.12207 · Cited by 236 · see citing works
Ahluwalia, N., Shea, B. S., & Tager, A. M. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201403-0509pp · Cited by 233 · see citing works
Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis
Kliment, C. R., & Oury, T. D. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.04.036 · Cited by 233 · see citing works
Metabolic features of the cell danger response
Naviaux, R. K. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.08.006 · Cited by 235 · see citing works
Roy, K., Wu, Y., Meitzler, J. L., Juhasz, A. N., Liu, H., Jiang, G., Lu, J., Antony, S., & Doroshow, J. H. (2015) · Clinical Science · doi:10.1042/cs20140542 · Cited by 231 · see citing works
Metformin attenuates lung fibrosis development via NOX4 suppression
Sato, N., Takasaka, N., Yoshida, M., Tsubouchi, K., Minagawa, S., Araya, J., Saito, N., Fujita, Y., Kurita, Y., Kobayashi, K., et al. (2016) · Respiratory Research · doi:10.1186/s12931-016-0420-x · Cited by 229 · see citing works
Mitochondrial dysfunction in fibrotic diseases
Li, X., Zhang, W. Y., Cao, Q., Wang, Z., Zhao, M., Xu, L., & Zhuang, Q. (2020) · Cell Death Discovery · doi:10.1038/s41420-020-00316-9 · Cited by 226 · see citing works
Myofibroblast differentiation and survival in fibrotic disease
Kis, K., Liu, X., & Hagood, J. S. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411001967 · Cited by 225 · see citing works
Oxidative Stress Is a Key Modulator in the Development of Nonalcoholic Fatty Liver Disease
Ma, Y., Lee, G., Heo, S.-Y., & Roh, Y. (2021) · Antioxidants · doi:10.3390/antiox11010091 · Cited by 225 · see citing works
TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review)
Ye, Z., & Hu, Y. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4965 · Cited by 226 · see citing works
Role of NADPH Oxidases in Liver Fibrosis
Paik, Y., Kim, J., Aoyama, T., Minicis, S. D., Bataller, R. A., & Brenner, D. A. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5619 · Cited by 221 · see citing works
Tian, J., Zhang, M., Suo, M., Liu, D., Wang, X., Liu, M. R., Pan, J., Jin, T., & An, F. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16601 · Cited by 215 · see citing works
Lan, T., Kisseleva, T., & Brenner, D. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129743 · Cited by 192 · see citing works
Boudreau, H. E., Casterline, B. W., Rada, B., Korzeniowska, A., & Leto, T. L. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.06.016 · Cited by 209 · see citing works
Novel therapeutic approaches for pulmonary fibrosis
Datta, A., Scotton, C. J., & Chambers, R. C. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01247.x · Cited by 203 · see citing works
Role of Oxidative Stress and the Microenvironment in Breast Cancer Development and Progression
Jezierska‐Drutel, A., Rosenzweig, S. A., & Neumann, C. A. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407190-2.00003-4 · Cited by 201 · see citing works
Targeting the Myofibroblastic Cancer-Associated Fibroblast Phenotype Through Inhibition of NOX4
Hanley, C. J., Mellone, M., Ford, K., Thirdborough, S. M., Mellows, T., Frampton, S. J., Smith, D. M., Harden, E., Szyndralewiez, C., Bullock, M., et al. (2018) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djx121 · Cited by 195 · see citing works
Global Methylation Patterns in Idiopathic Pulmonary Fibrosis
Rabinovich, E. I., Kapetanaki, M. G., Steinfeld, I., Gibson, K. F., Pandit, K. V., Yu, G., Zohar Yakhini, B., & Kaminski, N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033770 · Cited by 197 · see citing works
The Role of NADPH Oxidases (NOXs) in Liver Fibrosis and the Activation of Myofibroblasts
Liang, S., Kisseleva, T., & Brenner, D. A. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00017 · Cited by 197 · see citing works
Nowarski, R., Jackson, R., & Flavell, R. A. (2017) · Cell · doi:10.1016/j.cell.2016.11.040 · Cited by 191 · see citing works
PU.1 controls fibroblast polarization and tissue fibrosis
Wohlfahrt, T., Rauber, S., Uebe, S., Luber, M., Soare, A., Ekici, A., Weber, S., Matei, A.-E., Chen, C.-W., Maier, C., et al. (2019) · Nature · doi:10.1038/s41586-019-0896-x · Cited by 187 · see citing works
Mitochondrial quality control in pulmonary fibrosis
Larson‐Casey, J. L., He, C., & Carter, A. B. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101426 · Cited by 190 · see citing works
Han, C. Y., Umemoto, T., Omer, M., Den Hartigh, L. J., Chiba, T., LeBoeuf, R., Buller, C. L., Sweet, I. R., Pennathur, S., Abel, E. D., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.304998 · Cited by 187 · see citing works
Self-citationPM2.5 Exposure and Asthma Development: The Key Role of Oxidative Stress
Liu, K., Hua, S., & Song, L. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3618806 · Cited by 187 · see citing works
Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis
Wei, Y., Kim, T. J., Peng, D. H., Duan, D., Gibbons, D. L., Yamauchi, M., Jackson, J., Saux, C. J. L., Calhoun, C., Peters, J. I., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci94624 · Cited by 185 · see citing works
Molecular Pathways: Connecting Fibrosis and Solid Tumor Metastasis
Cox, T. R., & Erler, J. T. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1059 · Cited by 175 · see citing works
Sex Differences in Chronic Obstructive Pulmonary Disease Mechanisms
Barnes, P. J. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201512-2379ed · Cited by 176 · see citing works
From form to function: the role of Nox4 in the cardiovascular system
Chen, F., Haigh, S. B., Barman, S. A., & Fulton, D. J. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00412 · Cited by 172 · see citing works
Autophagy drives fibroblast senescence through MTORC2 regulation
Bernard, M., Yang, B., Migneault, F., Turgeon, J., Dieudé, M., Olivier, M., Cardin, G. B., El-Diwany, M., Underwood, K., Rodier, F., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1713640 · Cited by 174 · see citing works
Strategies for anti-fibrotic therapies
Rosenbloom, J., Mendoza, F. A., & Jiménez, S. A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.12.007 · Cited by 171 · see citing works
van der Vliet, A., Janssen-Heininger, Y. M. W., & Anathy, V. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.08.001 · Cited by 170 · see citing works
- Authors
- Hecker, L., Vittal, R., Jones, T., Jagirdar, R., Luckhardt, T. R., Horowitz, J. C., Pennathur, S., Martinez, F. J., & Thannickal, V. J.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Thannickal, Victor J
- ORCID
- Venue
- Nature Medicine
- Published
- 2009-08-23
- Volume
- 15
- Issue
- 9
- Pages
- 1077-1081
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC2743335
- OpenAlex
- W1966672647
- Cited by
- 852
- References
- 29
- Citations by year
- 2026: 34 · 2025: 33 · 2024: 38 · 2023: 51 · 2022: 38 · 2021: 59 · 2020: 64 · 2019: 51 · 2018: 44 · 2017: 52 · 2016: 72 · 2015: 56 · 2014: 65 · 2013: 47 · 2012: 59
- FWCI
- 42.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hr46162-13-0-1)
- National Heart, Lung, and Blood Institute (K08HL081059, N01HR046162, R01HL067967)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NOX4, idiopathic pulmonary fibrosis, myofibroblast activation, fibrogenesis, lung injury, reactive oxygen species, hydrogen peroxide, TGF-β1, Smad3, extracellular matrix synthesis, tissue repair, therapeutic target
- MeSH terms
- NADPH Oxidase 4, Animals, Cell Differentiation, Fibroblasts, Humans, Hydrogen Peroxide, Mice, Inbred C57BL, RNA, Messenger, NADPH Oxidases, RNA, Small Interfering, Mice, Smad3 Protein, Transforming Growth Factor beta1, Idiopathic Pulmonary Fibrosis, Lung Injury
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
