Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo
Open accessAbstract
Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Homologs of NADPH oxidases (NOXs) are major sources of ROS, but the exact role of the individual homologs in liver disease is unknown. Our goal was to determine the role of NOX4 in liver fibrosis induced by bile duct ligation (BDL) with the aid of the pharmacological inhibitor GKT137831, and genetic deletion of NOX4 in mice. GKT137831 was either applied for the full term of BDL (preventive arm) or started at 10 day postoperatively (therapeutic arm). Primary hepatic stellate cells (HSC) from control mice with and without BDL were analyzed and the effect of NOX4 inhibition on HSC activation was also studied. FasL or TNFα/actinomycin D-induced apoptosis was studied in wild-type and NOX4(-/-) hepatocytes. NOX4 was upregulated by a TGF-β/Smad3-dependent mechanism in HSC. Downregulation of NOX4 decreased ROS production and the activation of NOX4(-/-) HSC was attenuated. NOX4(-/-) hepatocytes were more resistant to FasL or TNFα/actinomycin D-induced apoptosis. Similarly, after pharmacological NOX4 inhibition, ROS production, the expression of fibrogenic markers, and hepatocyte apoptosis were reduced. NOX4 was expressed in human livers with stage 2-3 autoimmune hepatitis. Fibrosis was attenuated by the genetic deletion of NOX4. BDL mice gavaged with GKT137831 in the preventive or the therapeutic arm displayed less ROS production, significantly attenuated fibrosis, and decreased hepatocyte apoptosis. In conclusion, NOX4 plays a key role in liver fibrosis. GKT137831 is a potent inhibitor of fibrosis and hepatocyte apoptosis; therefore, it is a promising therapeutic agent for future translational studies.
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?
GKT-136901 and GKT-137831 are the first inhibitors suitable for oral administration, and currently GKT-137831 is in phase 2 clinical trials.
“GKT-136901 and GKT-137831 (FIGURE 10) are the first inhibitors suitable for oral administration, and currently GKT-137831 is in phase 2 clinical trials (472).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [472]
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
Mechanisms of Hepatic Fibrogenesis
Friedman, S. L. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.003 · Cited by 2,640 · see citing works
Pathogenesis of Liver Fibrosis
Hernandez-Gea, V., & Friedman, S. L. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130246 · Cited by 1,809 · see citing works
NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury
Hecker, L., Vittal, R., Jones, T., Jagirdar, R., Luckhardt, T. R., Horowitz, J. C., Pennathur, S., Martinez, F. J., & Thannickal, V. J. (2009) · Nature Medicine · doi:10.1038/nm.2005 · Cited by 852 · see citing works
Guicciardi, M. E., Deussing, J. M., Miyoshi, H., Bronk, S. F., Svingen, P. A., Peters, C., Kaufmann, S. H., & Gores, G. J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9914 · Cited by 710 · see citing works
Nox4 Is a Protective Reactive Oxygen Species Generating Vascular NADPH Oxidase
Schröder, K., Zhang, M., Benkhoff, S., Mieth, A., Pliquett, R., Kosowski, J., Kruse, C., Luedike, P., Michaelis, U. R., Weissmann, N., et al. (2012) · Circulation Research · doi:10.1161/circresaha.112.267054 · Cited by 622 · see citing works
Self-citationMechanisms of Disease Progression in Nonalcoholic Fatty Liver Disease
Jou, J. H., Choi, S. S., & Diehl, A. M. (2008) · Seminars in Liver Disease · doi:10.1055/s-0028-1091981 · Cited by 482 · 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
Gene Expression Profiles During Hepatic Stellate Cell Activation in Culture and In Vivo
Minicis, S. D., Seki, E., Uchinami, H., Kluwe, J., Zhang, Y., Brenner, D. A., & Schwabe, R. F. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.02.033 · Cited by 425 · see citing works
Zhan, S.-S., Jiang, J. X., Wu, J., Halsted, C., Friedman, S. L., Zern, M. A., & Torok, N. J. (2006) · Hepatology · doi:10.1002/hep.21093 · Cited by 284 · see citing works
Self-citationInvolvement of NADPH Oxidase Isoforms and Src Family Kinases in CD95-dependent Hepatocyte Apoptosis
Reinehr, R., Becker, S., Eberle, A., Grether‐Beck, S., & Häussinger, D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414361200 · Cited by 246 · see citing works
Laleu, 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
Self-citationCarmona‐Cuenca, I., Roncero, C., Sancho, P., Caja, L., Fausto, N., Fernández, M., & Fabregat, I. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.07.021 · Cited by 222 · see citing works
Nieto, N., Friedman, S. L., & Cederbaum, A. I. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110506200 · Cited by 208 · see citing works
Paik, Y., Iwaisako, K., Seki, E., Inokuchi, S., Schnabl, B., Österreicher, C. H., Kisseleva, T., & Brenner, D. A. (2011) · Hepatology · doi:10.1002/hep.24281 · Cited by 195 · see citing works
de Mochel, N. S. R., Seronello, S., Wang, S. H., Ito, C., Zheng, J. X., Liang, J. T., Lambeth, D. J., & Choi, J. (2010) · Hepatology · doi:10.1002/hep.23671 · Cited by 183 · see citing works
Jiang, J. X., Mikami, K., Venugopal, S. K., Li, Y., & Torok, N. J. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.03.024 · Cited by 155 · see citing works
Self-citationJiang, J. X., Venugopal, S. K., Serizawa, N., Chen, X., Scott, F., Li, Y., Adamson, R. H., Devaraj, S., Shah, V. H., Gershwin, M. E., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.05.074 · Cited by 120 · see citing works
Self-citationCui, W., Matsuno, K., Iwata, K., Ibi, M., Matsumoto, M., Zhang, J., Zhu, K., Katsuyama, M., Torok, N. J., & Yabe‐Nishimura, C. (2011) · Hepatology · doi:10.1002/hep.24465 · Cited by 113 · see citing works
Purification of rat hepatic stellate cells by side scatter-activated cell sorting
Geerts, A. E., Niki, T., Hellemans, K., Craemer, D. D., Berg, K. V. D., Lazou, J.-M., Stangé, G. M., Winkel, M. V. D., & Bleser, P. D. (1998) · Hepatology · doi:10.1002/hep.510270238 · Cited by 107 · see citing works
Oxidative and Nitrosative Stress and Fibrogenic Response
Urtasun, R., de la Rosa, L. C., & Nieto, N. (2008) · Clinics in Liver Disease · doi:10.1016/j.cld.2008.07.005 · Cited by 99 · see citing works
Spencer, N. Y., Yan, Z., Boudreau, R. L., Zhang, Y., Luo, M., Li, Q., Tian, X., Shah, A. M., Davisson, R. L., Davidson, B. L., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.193821 · Cited by 97 · see citing works
Sancho, P., Bertrán, E., Caja, L., Carmona‐Cuenca, I., Murillo, M. M., & Fabregat, I. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.09.003 · Cited by 83 · see citing works
Gaggini, F., Laleu, B., Orchard, M., Fioraso-Cartier, L., Cagnon, L., Houngninou-Molango, S., Gradia, A., Duboux, G., Merlot, C., Heitz, F., et al. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.10.016 · Cited by 79 · see citing works
Self-citationMehal, W. Z., & Imaeda, A. B. (2010) · Seminars in Liver Disease · doi:10.1055/s-0030-1255352 · Cited by 70 · see citing works
Baskin-Bey, E. S., Huang, W., Ishimura, N., Isomoto, H., Bronk, S. F., Braley, K. E., Craig, R. W., Moore, D. D., & Gores, G. J. (2006) · Hepatology · doi:10.1002/hep.21236 · Cited by 54 · see citing works
Mohamadnejad, M., Sohail, M. A., Watanabe, A., Krause, D. S., Swenson, S. E., & Mehal, W. Z. (2009) · Hepatology · doi:10.1002/hep.23389 · Cited by 27 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [26]Aoyama TPY Watanabe S Brenner D A critical role for the NADPH oxidase (NOX) in experimental liver fibrosis Hepatology Elsevier 2011 184
Cited by
Sorted by citations
Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives
Roehlen, N., Crouchet, E., & Baumert, T. F. (2020) · Cells · doi:10.3390/cells9040875 · Cited by 1,237 · see citing works
Reciprocal 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 710 · see citing works
Molecular pathways of nonalcoholic fatty liver disease development and progression
Bessone, F., Razori, M. V., & Roma, M. G. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2947-0 · Cited by 625 · see citing works
Sources 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
NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets
Zhang, Y., Murugesan, P., Huang, K., & Cai, H. “. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0260-8 · Cited by 546 · 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
Oxidative Stress in Liver Pathophysiology and Disease
Allameh, A., Niayesh‐Mehr, R., Aliarab, A., Sebastiani, G., & Pantopoulos, K. (2023) · Antioxidants · doi:10.3390/antiox12091653 · Cited by 565 · 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
Mieli‐Vergani, G., Vergani, D., Czaja, A. J., Manns, M. P., Krawitt, E. L., Vierling, J. M., Lohse, A. W., & Montaño‐Loza, A. J. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.17 · Cited by 471 · see citing works
Mechanisms of liver fibrosis and its role in liver cancer
Dhar, D., Baglieri, J., Kisseleva, T., & Brenner, D. A. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370219898141 · Cited by 440 · see citing works
NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus–Accelerated Atherosclerosis
Gray, S. P., Di Marco, E., Okabe, J., Szyndralewiez, C., Heitz, F., Montezano, A. C., de Haan, J. B., Koulis, C., El-Osta, A., Andrews, K. L., et al. (2013) · Circulation · doi:10.1161/circulationaha.112.132159 · Cited by 386 · see citing works
Self-citationCellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update
Elpek, G. Ö. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i23.7260 · Cited by 384 · see citing works
Excess TGF-β mediates muscle weakness associated with bone metastases in mice
Waning, D. L., Mohammad, K. S., Reiken, S. R., Xie, W., Andersson, D. C., John, S. K., Chiechi, A., Wright, L. E., Umanskaya, A., Niewolna, M., et al. (2015) · Nature Medicine · doi:10.1038/nm.3961 · Cited by 380 · see citing works
The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders
Tarafdar, A., & Pula, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123824 · Cited by 373 · see citing works
Jha, J. C., Gray, S. P., Barit, D., Okabe, J., El-Osta, A., Namikoshi, T., Thallas-Bonke, V., Wingler, K., Szyndralewiez, C., Heitz, F., et al. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013070810 · Cited by 352 · see citing works
Self-citationTransforming 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
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
Self-citationMorry, J., Ngamcherdtrakul, W., & Yantasee, W. (2016) · Redox Biology · doi:10.1016/j.redox.2016.12.011 · Cited by 332 · 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
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
Liver fibrosis: Pathophysiology and clinical implications
Berumen, J. A., Baglieri, J., Kisseleva, T., & Mekeel, K. L. (2020) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1499 · Cited by 276 · see citing works
Kim, K.-H., Chen, C.-C., Monzon, R. I., & Lau, L. F. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00049-13 · Cited by 261 · 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 227 · 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
Vendrov, A. E., Vendrov, K. C., Smith, A., Yuan, J., Sumida, A., Robidoux, J., Runge, M. S., & Madamanchi, N. R. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6221 · Cited by 219 · see citing works
Liver Fibrosis: Therapeutic Targets and Advances in Drug Therapy
Tan, Z., Sun, H., Xue, T., Gan, C., Liu, H., Xie, Y., Yao, Y., & Ye, T. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.730176 · Cited by 220 · see citing works
Lan, T., Kisseleva, T., & Brenner, D. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129743 · Cited by 192 · see citing works
Dissecting fibrosis: therapeutic insights from the small-molecule toolbox
Nanthakumar, C. B., Hatley, R. J. D., Lemma, S., Gauldie, J., Marshall, R. P., & Macdonald, S. J. F. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4592 · Cited by 206 · see citing works
The Role of NADPH Oxidases (NOXs) in Liver Fibrosis and the Activation of Myofibroblasts
Liang, S., Kisseleva, T., & Brenner, D. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00017 · Cited by 192 · see citing works
Gorin, Y., Cavaglieri, R. C., Khazim, K., Lee, D.-Y., Bruno, F., Thakur, S., Fanti, P., Szyndralewiez, C., Barnes, J. L., Block, K., et al. (2015) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00396.2014 · Cited by 183 · see citing works
Self-citationBettaieb, A., Jiang, J. X., Sasaki, Y., Chao, T.-I., Kiss, Z., Chen, X., Tian, J., Katsuyama, M., Yabe-Nishimura, C., Xi, Y., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.009 · Cited by 167 · see citing works
Self-citationSancho, P., Mainez, J., Crosas-Molist, E., Roncero, C., Fernández-Rodríguez, C., Pinedo, F., Huber, H., Eferl, R., Mikulits, W., & Fabregat, I. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045285 · Cited by 157 · see citing works
Therapeutic potential of nadph oxidase 1/4 inhibitors
Teixeira, G., Szyndralewiez, C., Molango, S., Carnesecchi, S., Heitz, F., Wiesel, P., & Wood, J. M. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13532 · Cited by 163 · see citing works
Self-citationReversal of liver cirrhosis: current evidence and expectations
Jung, Y. K., & Yim, H. J. (2017) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2016.268 · Cited by 152 · see citing works
Role of NADPH oxidases in the redox biology of liver fibrosis
Crosas‐Molist, E., & Fabregat, I. (2015) · Redox Biology · doi:10.1016/j.redox.2015.07.005 · Cited by 149 · see citing works
The nox4 inhibitor gkt137831 attenuates hypoxia-induced pulmonary vascular cell proliferation
Green, D. E., Murphy, T. C., Kang, B.-Y., Kleinhenz, J. M., Szyndralewiez, C., Page, P., Sutliff, R. L., & Hart, C. M. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2011-0418oc · Cited by 146 · see citing works
Self-citationAmini‐Nik, S., Yousuf, Y., & Jeschke, M. G. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.07.017 · Cited by 147 · see citing works
Nox4 and diabetic nephropathy: With a friend like this, who needs enemies?
Gorin, Y. C., & Block, K. L. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.014 · Cited by 134 · see citing works
Physiological and pathological functions of NADPH oxidases during myocardial ischemia–reperfusion
Matsushima, S., Tsutsui, H., & Sadoshima, J. (2014) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2014.03.003 · Cited by 132 · see citing works
Targeting Oxidative Stress as a Therapeutic Approach for Idiopathic Pulmonary Fibrosis
Estornut, C., Milara, J., Bayarri, M. A., Belhadj, N., & Cortijo, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.794997 · Cited by 135 · see citing works
NADPH Oxidase, NOX1, Mediates Vascular Injury in Ischemic Retinopathy
Wilkinson‐Berka, J. L., Deliyanti, D., Rana, I., Miller, A. G., Agrotis, A., Armani, R., Szyndralewiez, C., Wingler, K., Touyz, R. M., Cooper, M. E., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5357 · Cited by 122 · see citing works
Self-citationNox as a target for diabetic complications
Gorin, Y. C., & Block, K. L. (2013) · Clinical Science · doi:10.1042/cs20130065 · Cited by 119 · see citing works
Updates of reactive oxygen species in melanoma etiology and progression
Liu, F., Dellinger, R. W., & Meyskens, F. L. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.04.007 · Cited by 116 · see citing works
An Inhibitor of NADPH Oxidase-4 Attenuates Established Pulmonary Fibrosis in a Rodent Disease Model
Jarman, E. R., Khambata, V. S., Cope, C. L., Jones, P. L., Roger, J., Ye, L. Y., Duggan, N., Head, D., Pearce, A. C., Press, N. J., et al. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0174oc · Cited by 114 · see citing works
Bernard, K. F., Logsdon, N. J., Miguel, V., Benavides, G. A., Zhang, J., Carter, A. B., Darley-Usmar, V. M., & Thannickal, V. J. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.752261 · Cited by 115 · see citing works
Gray, S. P., Jha, J. C., Kennedy, K., van Bommel, E. J. M., Chew, P., Szyndralewiez, C., Touyz, R. M., Schmidt, H. H. H. W., Cooper, M. E., & Jandeleit-Dahm, K. A. M. (2017) · Diabetologia · doi:10.1007/s00125-017-4215-5 · Cited by 109 · see citing works
Self-citationNADPH oxidases: redox regulation of cell homeostasis and disease
Kračun, D., Lopes, L. R., Cifuentes-Pagano, E., & Pagano, P. J. (2025) · Physiological Reviews · doi:10.1152/physrev.00034.2023 · Cited by 104 · see citing works
Cai, S., Yang, R., Li, Y., Ning, Z., Zhang, L., Zhou, G.-S., Luo, W., Li, D.-H., Chen, Y., Pan, M., et al. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6498 · Cited by 103 · see citing works
Hu, B., & Phan, S. H. (2012) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e32835b1352 · Cited by 98 · see citing works
Nadph oxidase 1 in liver macrophages promotes inflammation and tumor development in mice
Liang, S., Ma, H.-Y., Zhong, Z., Dhar, D., Liu, X., Xu, J., Koyama, Y., Nishio, T., Karin, D., Karin, G., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.11.019 · Cited by 92 · see citing works
NOXious signaling in pain processing
Kallenborn-Gerhardt, W., Schröder, K., Geißlinger, G., & Schmidtko, A. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.11.001 · Cited by 91 · see citing works
Self-citationThe NADPH oxidase NOX4 inhibits hepatocyte proliferation and liver cancer progression
Crosas‐Molist, E., Bertrán, E., Sancho, P., López‐Luque, J., Fernando, J., Sánchez, A., Fernández, M., Navarro, E., & Fabregat, I. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.01.040 · Cited by 90 · see citing works
Oxidative stress and hepatic Nox proteins in chronic hepatitis C and hepatocellular carcinoma
Choi, J., Corder, N. L. B., Koduru, B., & Wang, Y. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.04.020 · Cited by 86 · see citing works
Targeting oxidative stress-mediated regulated cell death as a vulnerability in cancer
Chen, D., Guo, Z., Yao, L., Sun, Y., Dian, Y., Zhao, D., Ke, Y., Zeng, F., Zhang, C., Deng, G., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103686 · Cited by 88 · see citing works
Cheng, A. J., Bruton, J. D., Lanner, J. T., & Westerblad, H. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.279398 · Cited by 86 · see citing works
Linking RAGE and Nox in diabetic micro- and macrovascular complications
Koulis, C., Watson, A. M. D., Gray, S. P., & Jandeleit-Dahm, K. A. M. (2015) · Diabetes & Metabolism · doi:10.1016/j.diabet.2015.01.006 · Cited by 86 · see citing works
The Quest for Selective Nox Inhibitors and Therapeutics: Challenges, Triumphs and Pitfalls
Cifuentes-Pagano, E., Meijles, D. N., & Pagano, P. J. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5620 · Cited by 84 · see citing works
SIRT1–NOX4 signaling axis regulates cancer cachexia
Dasgupta, A., Shukla, S. K., Vernucci, E., King, R. J., Abrego, J., Mulder, S. E., Mullen, N. J., Graves, G., Buettner, K. B., Thakur, R. K., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190745 · Cited by 84 · see citing works
HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells
Ivanov, A. V., Smirnova, O. A., Petrushanko, I. Y., Ivanova, O. N., Karpenko, I. L., Alekseeva, E., Sominskaya, I., Makarov, A. А., Bartosch, B., Kochetkov, S. N., et al. (2015) · Viruses · doi:10.3390/v7062745 · Cited by 83 · see citing works
Promising Therapy Candidates for Liver Fibrosis
Wang, P., Koyama, Y., Liu, X., Xu, J., Ma, H., Liang, S., Kim, I. H., Brenner, D. A., & Kisseleva, T. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00047 · Cited by 81 · see citing works
Invernizzi, P., Carbone, M., Jones, D., Levy, C., Little, N., Wiesel, P., Nevens, F., & the study investigators (2023) · Liver International · doi:10.1111/liv.15596 · Cited by 79 · see citing works
Shehzad, A., Parveen, S., Qureshi, M., Subhan, F., & Lee, Y. S. (2017) · Inflammation Research · doi:10.1007/s00011-017-1114-7 · Cited by 77 · see citing works
Inhibiting the Activity of NADPH Oxidase in Cancer
Konaté, M. M., Antony, S., & Doroshow, J. H. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8046 · Cited by 77 · see citing works
Duan, J., Gao, S., Tu, S., Lenahan, C., Shao, A., & Sheng, J. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6631805 · Cited by 76 · see citing works
NADPH Oxidases in Chronic Liver Diseases
Jiang, J. X., & Torok, N. J. (2014) · Advances in Hepatology · doi:10.1155/2014/742931 · Cited by 76 · see citing works
Self-citationDeliyanti, D., & Wilkinson‐Berka, J. L. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0363-z · Cited by 77 · see citing works
Pathophysiology of gadolinium-associated systemic fibrosis
Wagner, B., Drel, V. R., & Gorin, Y. C. (2016) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00166.2016 · Cited by 74 · see citing works
Antifibrotic Therapies in the Liver
Schuppan, D., & Mehal, W. Z. (2015) · Seminars in Liver Disease · doi:10.1055/s-0035-1550055 · Cited by 75 · see citing works
The rationale for targeting TGF ‐β in chronic liver diseases
Giannelli, G., Mikulits, W., Dooley, S., Fabregat, I., Moustakas, A., ten Dijke, P., Portincasa, P., Winter, P., Janssen, R. A. J., Leporatti, S., et al. (2016) · European Journal of Clinical Investigation · doi:10.1111/eci.12596 · Cited by 75 · see citing works
Ahmadian, E., Pennefather, P., Eftekhari, A., Heidari, R., & Eghbal, M. A. (2016) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2016.1207523 · Cited by 73 · see citing works
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis: A review
Mortezaee, K. (2018) · Cell Biochemistry and Function · doi:10.1002/cbf.3351 · Cited by 72 · see citing works
Somanna, N. K., Valente, A. J., Krenz, M., Fay, W. P., Delafontaine, P., & Chandrasekar, B. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.25210 · Cited by 71 · see citing works
TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis: Updated
Dewidar, B., Soukupová, J., Fabregat, I., & Dooley, S. (2015) · Current Pathobiology Reports · doi:10.1007/s40139-015-0089-8 · Cited by 71 · see citing works
Morry, J., Ngamcherdtrakul, W., Gu, S., Goodyear, S. M., Castro, D. J., Reda, M. M., Sangvanich, T., & Yantasee, W. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.07.005 · Cited by 71 · see citing works
Extracellular matrix remodelling in obesity and metabolic disorders
Musale, V., Wasserman, D. H., & Kang, L. (2023) · Life Metabolism · doi:10.1093/lifemeta/load021 · Cited by 76 · see citing works
Zhang, P., Yin, Y., Wang, T., Li, W., Li, C., Zeng, X., Yang, W., Zhang, R., Tang, Y., Shi, L., et al. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.11.033 · Cited by 69 · see citing works
Integrin β 1: A Mechanosignaling Sensor Essential for Connective Tissue Deposition by Fibroblasts
Leask, A. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0365 · Cited by 67 · see citing works
Torok, N. J., Dranoff, J. A., Schuppan, D., & Friedman, S. L. (2015) · Hepatology · doi:10.1002/hep.27720 · Cited by 70 · see citing works
Liver Injury and the Activation of the Hepatic Myofibroblasts
Jiang, J. X., & Torok, N. J. (2013) · Current Pathobiology Reports · doi:10.1007/s40139-013-0019-6 · Cited by 69 · see citing works
Self-citationNuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis
Swamy, S., Rajasekaran, N. S., & Thannickal, V. J. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.02.022 · Cited by 67 · see citing works
Davidson, M. D., Kukla, D. A., & Khetani, S. R. (2017) · Integrative Biology · doi:10.1039/c7ib00027h · Cited by 66 · see citing works
Thannickal, V. J., Jandeleit‐Dahm, K., Szyndralewiez, C., & Török, N. J. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17649 · Cited by 65 · see citing works
Self-citationUrsolic acid ameliorates CCl4‐induced liver fibrosis through the NOXs/ROS pathway
Gan, D., Zhang, W., Huang, C., Jiang, C., He, W., Wang, A., Li, B., & Zhu, X. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26541 · Cited by 65 · see citing works
Backstage players of fibrosis: NOX4, mTOR, HDAC, and S1P; companions of TGF-β
Jiménez‐Uribe, A. P., Gómez‐Sierra, T., Aparicio‐Trejo, O. E., Orozco‐Ibarra, M., & Pedraza‐Chaverrí, J. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110123 · Cited by 64 · see citing works
Spadoni, T., Svegliati, S., Amico, D., Albani, L., Moroncini, G., Avvedimento, E. V., & Gabrielli, A. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39084 · Cited by 64 · see citing works
Anti-fibrotic treatments for chronic liver diseases: The present and the future
Odagiri, N., Matsubara, T., Sato-Matsubara, M., Fujii, H., Enomoto, M., & Kawada, N. (2020) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2020.0187 · Cited by 63 · see citing works
Marco, E. D., Gray, S. P., & Jandeleit-Dahm, K. A. M. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00068 · Cited by 62 · see citing works
Greatorex, S., Kaur, S., Xirouchaki, C. E., Goh, P. K., Wiede, F., Genders, A., Tran, M., Jia, Y., Raajendiran, A., Brown, W., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci162533 · Cited by 50 · see citing works
Therapeutic pro-fibrogenic signaling pathways in fibroblasts
Cannito, S., Novo, E., & Parola, M. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.05.017 · Cited by 60 · see citing works
Piera-Velázquez, S., & Jiménez, S. A. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10204791 · Cited by 60 · see citing works
Sampson, N., Berger, P., & Zenzmaier, C. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/458276 · Cited by 60 · see citing works
Smirnova, O. A., Ivanova, O. N., Bartosch, B., Треворович, В.-Э. В., Mukhtarov, F., Kochetkov, S. N., & Ivanov, A. V. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/8341937 · Cited by 60 · see citing works
Artlett, C. M., & Thacker, J. D. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6148 · Cited by 59 · see citing works
The pathogenesis, models and therapeutic advances of primary biliary cholangitis
Li, H., Guan, Y., Han, C., Zhang, Y., Liu, Q., Wei, W., & Ma, Y. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111754 · Cited by 58 · see citing works
Zhou, S., Li, W., Shi, F., Zhou, Z.-W., Li, B., Zhang, K., Zhang, X., Ouyang, C., & Zhu, X. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s85426 · Cited by 58 · see citing works
Dietary Fisetin Supplementation Protects Against Alcohol‐Induced Liver Injury in Mice
Sun, Q., Zhang, W., Zhong, W. H., Sun, X., & Zhou, Z. (2016) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13172 · Cited by 58 · see citing works
Sun, Q., Zhang, W., Zhong, W. H., Sun, X., & Zhou, Z. (2016) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2016.09.009 · Cited by 56 · see citing works
The NOX1/4 Inhibitor GKT136901 as Selective and Direct Scavenger of Peroxynitrite
Schildknecht, S., Weber, A., Gerding, H., Pape, R., Robotta, M., Drescher, M., Marquardt, A., Daiber, A., Ferger, B., & Leist, M. (2013) · Current Medicinal Chemistry · doi:10.2174/09298673113209990179 · Cited by 55 · see citing works
NOX as a Therapeutic Target in Liver Disease
Matuz‐Mares, D., Vázquez‐Meza, H., & Vilchis‐Landeros, M. M. (2022) · Antioxidants · doi:10.3390/antiox11102038 · Cited by 55 · see citing works
Sampson, N., Berger, P., & Zenzmaier, C. (2014) · BioMed Research International · doi:10.1155/2014/131737 · Cited by 54 · see citing works
- Authors
- Jiang, J. X., Chen, X., Serizawa, N., Szyndralewiez, C., Page, P., Schröder, K., Brandes, R. P., Devaraj, S., & Török, N. J.
- Affiliations
- UC Davis Health (US)
- Genkyotex (Switzerland) (CH)
- Goethe University Frankfurt (DE)
- University of California Davis Medical Center (US)
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 53
- Issue
- 2
- Pages
- 289-296
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC3392471
- OpenAlex
- W2081975963
- Cited by
- 251
- References
- 26
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 3 · 2023: 24 · 2022: 15 · 2021: 18 · 2020: 17 · 2019: 15 · 2018: 13 · 2017: 21 · 2016: 20 · 2015: 33 · 2014: 21 · 2013: 20 · 2012: 7
- FWCI
- 16.41
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK083283, DK-083283, R01DK083283)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- liver fibrosis, hepatocyte apoptosis, GKT137831, NADPH oxidase, reactive oxygen species, bile duct ligation, hepatic stellate cell activation, TGF-β/Smad3 signaling, TNFα-induced apoptosis, autoimmune hepatitis, chronic liver injury
- MeSH terms
- NADPH Oxidase 1, NADPH Oxidase 4, Animals, Bile Ducts, Dactinomycin, Humans, Ligation, Liver, Liver Cirrhosis, NADH, NADPH Oxidoreductases, Pyrazoles, Pyridines, Pyridones, Signal Transduction, Transforming Growth Factor beta, Apoptosis, Gene Deletion, Reactive Oxygen Species, NADPH Oxidases, Hepatitis, Autoimmune, Hepatocytes, Pyrazolones, Mice, Rats, Smad3 Protein, Fas Ligand Protein, Hepatic Stellate Cells
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