Gene Symbol: Nox4
Description: NADPH oxidase 4
Alias: AI648021, NADPH oxidase 4, KOX-1, kidney oxidase-1, kidney superoxide-producing NADPH oxidase, renal NAD(P)H-oxidase, superoxide-generating NADPH oxidase 4
Species: mouse
Products:     Nox4

Top Publications

  1. Geiszt M, Kopp J, Varnai P, Leto T. Identification of renox, an NAD(P)H oxidase in kidney. Proc Natl Acad Sci U S A. 2000;97:8010-4 pubmed
  2. Kim K, Choi H, Yoon H, Kim I. Reactive oxygen species generated by NADPH oxidase 2 and 4 are required for chondrogenic differentiation. J Biol Chem. 2010;285:40294-302 pubmed publisher
    ..of Nox1 and Nox2 was increased upon differentiation of ATDC5 cells and primary mouse chondrocytes, whereas that of Nox4, which was relatively high initially, was decreased gradually during chondrogenesis...
  3. Brewer A, Murray T, Arno M, Zhang M, Anilkumar N, Mann G, et al. Nox4 regulates Nrf2 and glutathione redox in cardiomyocytes in vivo. Free Radic Biol Med. 2011;51:205-15 pubmed publisher
    NADPH oxidase-4 (Nox4) is an important modulator of redox signaling that is inducible at the level of transcriptional expression in multiple cell types...
  4. Schröder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J, et al. Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. Circ Res. 2012;110:1217-25 pubmed publisher
    The function of Nox4, a source of vascular H(2)O(2), is unknown. Other Nox proteins were identified as mediators of endothelial dysfunction...
  5. Schröder K, Wandzioch K, Helmcke I, Brandes R. Nox4 acts as a switch between differentiation and proliferation in preadipocytes. Arterioscler Thromb Vasc Biol. 2009;29:239-45 pubmed publisher
    ..Insulin also stimulates reactive oxygen species (ROS) production, and the NADPH oxidases Nox1 and Nox4 are important sources of ROS...
  6. Li N, Li B, Brun T, Deffert Delbouille C, Mahiout Z, Daali Y, et al. NADPH oxidase NOX2 defines a new antagonistic role for reactive oxygen species and cAMP/PKA in the regulation of insulin secretion. Diabetes. 2012;61:2842-50 pubmed publisher
    ..Results also show reciprocal inhibition between the cAMP/PKA pathway and ROS. ..
  7. Li J, Stouffs M, Serrander L, Banfi B, Bettiol E, Charnay Y, et al. The NADPH oxidase NOX4 drives cardiac differentiation: Role in regulating cardiac transcription factors and MAP kinase activation. Mol Biol Cell. 2006;17:3978-88 pubmed
    ..Down-regulation of NOX4, the major NOX isoform present during early stages of differentiation, suppressed cardiogenesis...
  8. Murray T, Smyrnias I, Shah A, Brewer A. NADPH oxidase 4 regulates cardiomyocyte differentiation via redox activation of c-Jun protein and the cis-regulation of GATA-4 gene transcription. J Biol Chem. 2013;288:15745-59 pubmed publisher
    b>NADPH oxidase 4 (Nox4) generates reactive oxygen species (ROS) that can modulate cellular phenotype and function in part through the redox modulation of the activity of transcription factors...
  9. Byrne J, Grieve D, Bendall J, Li J, Gove C, Lambeth J, et al. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ Res. 2003;93:802-5 pubmed
    ..Myocardial expression of an alternative gp91phox isoform, Nox4, was upregulated after aortic constriction in gp91phox-/- mice...

More Information


  1. Carnesecchi S, Deffert C, Donati Y, Basset O, Hinz B, Preynat Seauve O, et al. A key role for NOX4 in epithelial cell death during development of lung fibrosis. Antioxid Redox Signal. 2011;15:607-19 pubmed publisher linked to oxidative stress, possibly generated by the reactive oxygen species (ROS) generating NADPH oxidase NOX4. Epithelial cell death is a crucial early step in the development of the disease, followed only later by the ..
  2. Takac I, Schröder K, Zhang L, Lardy B, Anilkumar N, Lambeth J, et al. The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J Biol Chem. 2011;286:13304-13 pubmed publisher
    In contrast to the NADPH oxidases Nox1 and Nox2, which generate superoxide (O(2)(·-)), Nox4 produces hydrogen peroxide (H(2)O(2))...
  3. Nlandu Khodo S, Dizin E, Sossauer G, Szanto I, Martin P, Feraille E, et al. NADPH-oxidase 4 protects against kidney fibrosis during chronic renal injury. J Am Soc Nephrol. 2012;23:1967-76 pubmed publisher
    NADPH oxidases synthesize reactive oxygen species that may participate in fibrosis progression. NOX4 and NOX2 are NADPH oxidases expressed in the kidneys, with the former being the major renal isoform, but their contribution to renal ..
  4. Lee J, Joo J, Kim J, Lim H, Kim S, Curtiss L, et al. Interaction of NADPH oxidase 1 with Toll-like receptor 2 induces migration of smooth muscle cells. Cardiovasc Res. 2013;99:483-93 pubmed publisher
  5. Babelova A, Avaniadi D, Jung O, Fork C, Beckmann J, Kosowski J, et al. Role of Nox4 in murine models of kidney disease. Free Radic Biol Med. 2012;53:842-53 pubmed publisher
    b>Nox4 is a hydrogen peroxide-producing NADPH oxidase highly expressed in the kidney which has been linked to epithelial cell injury and diabetic-induced cellular dysfunction in cultured cells...
  6. Chamseddine A, Miller F. Gp91phox contributes to NADPH oxidase activity in aortic fibroblasts but not smooth muscle cells. Am J Physiol Heart Circ Physiol. 2003;285:H2284-9 pubmed
    ..Finally, deficiency of gp91phox did not alter expression of the gp91phox homolog NOX4 in isolated FB...
  7. Nadworny A, Guruju M, Poor D, Doran R, Sharma R, Kotlikoff M, et al. Nox2 and Nox4 influence neonatal c-kit(+) cardiac precursor cell status and differentiation. Am J Physiol Heart Circ Physiol. 2013;305:H829-42 pubmed publisher
    ..ROS generator Nox2 and its subunit p67(phox) in c-kit(+) CPCs under basal conditions but upregulation of Nox2 and Nox4 over the course of differentiation...
  8. Gray S, Di Marco E, Okabe J, Szyndralewiez C, Heitz F, Montezano A, et al. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation. 2013;127:1888-902 pubmed publisher
    ..Deletion of Nox1, but not Nox4, had a profound antiatherosclerotic effect correlating with reduced reactive oxygen species formation, attenuation ..
  9. Mandal C, Ganapathy S, Gorin Y, Mahadev K, Block K, Abboud H, et al. Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation. Biochem J. 2011;433:393-402 pubmed publisher
    ..We demonstrate that 2T3 pre-osteoblasts predominantly express the Nox4 isotype of NAD(P)H oxidase. To extend this finding, we tested the functional effects of Nox4...
  10. Anilkumar N, Weber R, Zhang M, Brewer A, Shah A. Nox4 and nox2 NADPH oxidases mediate distinct cellular redox signaling responses to agonist stimulation. Arterioscler Thromb Vasc Biol. 2008;28:1347-54 pubmed publisher
    The NADPH oxidase isoforms Nox2 and Nox4 are coexpressed in many cell types and are implicated in agonist-stimulated redox-sensitive signal transduction...
  11. Hecker L, Vittal R, Jones T, Jagirdar R, Luckhardt T, Horowitz J, et al. NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nat Med. 2009;15:1077-81 pubmed publisher
    ..Here we report a role for the NOX4 isoform in tissue repair functions of myofibroblasts and fibrogenesis...
  12. Ago T, Kuroda J, Pain J, Fu C, Li H, Sadoshima J. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res. 2010;106:1253-64 pubmed publisher
    NADPH oxidases are a major source of superoxide (O(2)(-)) in the cardiovascular system. The function of Nox4, a member of the Nox family of NADPH oxidases, in the heart is poorly understood...
  13. Sedeek M, Callera G, Montezano A, Gutsol A, Heitz F, Szyndralewiez C, et al. Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy. Am J Physiol Renal Physiol. 2010;299:F1348-58 pubmed publisher
    ..Expression (gene and protein) of Nox4, p22(phox), and p47(phox), but not Nox1 or Nox2, was increased in kidney cortex, but not medulla, from db/db vs...
  14. Jiang J, Chen X, Serizawa N, Szyndralewiez C, Page P, Schröder K, et al. Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo. Free Radic Biol Med. 2012;53:289-96 pubmed publisher
    ..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 ..
  15. Liu R, Choi J, Wu J, Gaston Pravia K, Lewis K, Brand J, et al. Oxidative modification of nuclear mitogen-activated protein kinase phosphatase 1 is involved in transforming growth factor beta1-induced expression of plasminogen activator inhibitor 1 in fibroblasts. J Biol Chem. 2010;285:16239-47 pubmed publisher
    ..In this study, we show that TGF-beta1 stimulates NADPH oxidase 4 (Nox4) expression and ROS generation in the nucleus of murine embryo fibroblasts (NIH3T3 cells)...
  16. Vallet P, Charnay Y, Steger K, Ogier Denis E, Kovari E, Herrmann F, et al. Neuronal expression of the NADPH oxidase NOX4, and its regulation in mouse experimental brain ischemia. Neuroscience. 2005;132:233-8 pubmed
    ..The present study was carried out to examine the expression of NOX4, one of the new NADPH oxidase isoforms in a mouse model of focal permanent brain ischemia...
  17. Zhang M, Brewer A, Schröder K, Santos C, Grieve D, Wang M, et al. NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis. Proc Natl Acad Sci U S A. 2010;107:18121-6 pubmed publisher
    ..Here we report that NADPH oxidase-4 (Nox4) facilitates cardiac adaptation to chronic stress...
  18. Craige S, Chen K, Pei Y, Li C, Huang X, Chen C, et al. NADPH oxidase 4 promotes endothelial angiogenesis through endothelial nitric oxide synthase activation. Circulation. 2011;124:731-40 pubmed publisher
    ..b>NADPH oxidase 4 (Nox4) is a reactive oxygen species-producing enzyme that is highly expressed in the endothelium, yet its ..
  19. Mittal M, Roth M, Konig P, Hofmann S, Dony E, Goyal P, et al. Hypoxia-dependent regulation of nonphagocytic NADPH oxidase subunit NOX4 in the pulmonary vasculature. Circ Res. 2007;101:258-67 pubmed
    ..NOX1, NOXA1, NOXO1, p22phox, p47phox, p40phox, p67phox, NOX2, and NOX4 were present in mouse lung tissue...
  20. Yeh Y, Kuo C, Chang G, Qi X, Nattel S, Chen W. Nicotinamide adenine dinucleotide phosphate oxidase 4 mediates the differential responsiveness of atrial versus ventricular fibroblasts to transforming growth factor-?. Circ Arrhythm Electrophysiol. 2013;6:790-8 pubmed publisher
    ..Nicotinamide adenine dinucleotide phosphate oxidase inhibitors and small-interfering RNA for Nox4 eliminated TGF-?-induced difference between atrial and ventricular fibroblasts, suggesting the crucial role of Nox4 ..
  21. Xu S, Chamseddine A, Carrell S, Miller F. Nox4 NADPH oxidase contributes to smooth muscle cell phenotypes associated with unstable atherosclerotic plaques. Redox Biol. 2014;2:642-50 pubmed publisher
    ..Specifically, Nox1 expression was increased early and decreased with lesion progression, while induction of Nox4 was a late event. Nox2 and p22(phox) were elevated throughout lesion development...
  22. Weissmann N, Sydykov A, Kalwa H, Storch U, Fuchs B, Mederos y Schnitzler M, et al. Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice. Nat Commun. 2012;3:649 pubmed publisher
    ..This mechanism highlights novel pharmacological targets for the treatment of LIRE. ..
  23. Bretón Romero R, Acin Perez R, Rodriguez Pascual F, Martinez Molledo M, Brandes R, Rial E, et al. Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells. Biochim Biophys Acta. 2014;1843:2403-13 pubmed publisher
    ..Our data support a novel and active role for mitochondria in endothelial cells as active players, able to transduce the mechanical force of shear stress in the vascular endothelium into a biological response. ..
  24. Kuroda J, Ago T, Matsushima S, Zhai P, Schneider M, Sadoshima J. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci U S A. 2010;107:15565-70 pubmed publisher
    NAD(P)H oxidases (Noxs) produce O(2)(-) and play an important role in cardiovascular pathophysiology. The Nox4 isoform is expressed primarily in the mitochondria in cardiac myocytes...
  25. Smyrnias I, Zhang X, Zhang M, Murray T, Brandes R, Schröder K, et al. Nicotinamide adenine dinucleotide phosphate oxidase-4-dependent upregulation of nuclear factor erythroid-derived 2-like 2 protects the heart during chronic pressure overload. Hypertension. 2015;65:547-53 pubmed publisher
  26. Xi G, Shen X, Wai C, Vilas C, Clemmons D. Hyperglycemia stimulates p62/PKCζ interaction, which mediates NF-κB activation, increased Nox4 expression, and inflammatory cytokine activation in vascular smooth muscle. FASEB J. 2015;29:4772-82 pubmed publisher
    ..Prior studies showed that hyperglycemia stimulated NADPH oxidase 4 (Nox4) synthesis, and IGF-I facilitated its recruitment to a signaling complex where it oxidized src, leading ..
  27. Lan T, Kisseleva T, Brenner D. Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice through Inhibition of Hepatic Stellate Cell Activation. PLoS ONE. 2015;10:e0129743 pubmed publisher
    ..The effect of NOX1 and NOX4 deficiency in liver fibrosis is unclear, and has never been directly compared...
  28. Zhao Q, Viswanadhapalli S, Williams P, Shi Q, Tan C, Yi X, et al. NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating Akt/mTOR and NFκB signaling pathways. Circulation. 2015;131:643-55 pubmed publisher
    b>NADPH oxidase 4 (Nox4) has been implicated in cardiac remodeling, but its precise role in cardiac injury remains controversial...
  29. Peters D, Vadász I, Wujak L, Wygrecka M, Olschewski A, Becker C, et al. TGF-? directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury. Proc Natl Acad Sci U S A. 2014;111:E374-83 pubmed publisher
    ..TGF-? rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1?, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of ?ENaC, the subunit responsible for cell-..
  30. Xi G, Shen X, Wai C, Clemmons D. Recruitment of Nox4 to a plasma membrane scaffold is required for localized reactive oxygen species generation and sustained Src activation in response to insulin-like growth factor-I. J Biol Chem. 2013;288:15641-53 pubmed publisher
    b>Nox4-derived ROS is increased in response to hyperglycemia and is required for IGF-I-stimulated Src activation. This study was undertaken to determine the mechanism by which Nox4 mediates sustained Src activation...
  31. Ding H, Hashem M, Triggle C. Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: changes in expression of NADPH oxidase subunits and eNOS. Eur J Pharmacol. 2007;561:121-8 pubmed
    ..In the mesenteric arteries the expression of nox4 (4 weeks) and gp91phox (nox2) (8 weeks) subunits of NADPH oxidase from streptozotocin-apoE(-/-) were enhanced as ..
  32. Feraille E, Dizin E, Roth I, Derouette J, Szanto I, Martin P, et al. NADPH oxidase 4 deficiency reduces aquaporin-2 mRNA expression in cultured renal collecting duct principal cells via increased PDE3 and PDE4 activity. PLoS ONE. 2014;9:e87239 pubmed publisher
    ..NAPDH oxidase 4 (NOX4) represents a major source of reactive oxygen species (ROS) in the kidney...
  33. Infanger D, Cao X, Butler S, Burmeister M, Zhou Y, Stupinski J, et al. Silencing nox4 in the paraventricular nucleus improves myocardial infarction-induced cardiac dysfunction by attenuating sympathoexcitation and periinfarct apoptosis. Circ Res. 2010;106:1763-74 pubmed publisher
    ..Real-time PCR revealed that Nox4 was the most abundantly expressed Nox in PVN under basal conditions...
  34. Chan E, Peshavariya H, Liu G, Jiang F, Lim S, Dusting G. Nox4 modulates collagen production stimulated by transforming growth factor ?1 in vivo and in vitro. Biochem Biophys Res Commun. 2013;430:918-25 pubmed publisher
    ..We hypothesized that NADPH oxidase isoform Nox4 facilitates the stimulatory effects of the profibrotic cytokine transforming growth factor (TGF) ?(1) on collagen ..
  35. Gordillo G, Biswas A, Khanna S, Pan X, Sinha M, Roy S, et al. Dicer knockdown inhibits endothelial cell tumor growth via microRNA 21a-3p targeting of Nox-4. J Biol Chem. 2014;289:9027-38 pubmed publisher
    ..These findings provide the first evidence establishing the significance of dicer and microRNA in promoting endothelial cell tumor growth in vivo. ..
  36. Kodama R, Kato M, Furuta S, Ueno S, Zhang Y, Matsuno K, et al. ROS-generating oxidases Nox1 and Nox4 contribute to oncogenic Ras-induced premature senescence. Genes Cells. 2013;18:32-41 pubmed publisher
    ..pathway, Ras oncogene up-regulated the expression of superoxide-generating oxidases, Nox1 in rat REF52 cells and Nox4 in primary human lung TIG-3 cells, leading to an increase in intracellular level of ROS...
  37. Distasi M, Mund J, Bohlen H, Miller S, Ingram D, Dalsing M, et al. Impaired compensation to femoral artery ligation in diet-induced obese mice is primarily mediated via suppression of collateral growth by Nox2 and p47phox. Am J Physiol Heart Circ Physiol. 2015;309:H1207-17 pubmed publisher
    ..49 ± 29%) and collateral diameter (151 ± 30% vs. 44 ± 17%). Vascular mRNA expression of p22(phox), Nox2, Nox4, and p47(phox) were all increased in DIO mice...
  38. Ford B, Eid A, Gooz M, Barnes J, Gorin Y, Abboud H. ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice. Am J Physiol Renal Physiol. 2013;305:F323-32 pubmed publisher
    ..inhibitor to ADAM17, TMI-005, we determined that ADAM17 activation results in increased type IV collagen, Nox4, and NADPH oxidase activity in the kidney cortex of diabetic mice...
  39. Al Harbi N, Nadeem A, Ansari M, Al Harbi M, Alotaibi M, Alsaad A, et al. Psoriasis-like inflammation leads to renal dysfunction via upregulation of NADPH oxidases and inducible nitric oxide synthase. Int Immunopharmacol. 2017;46:1-8 pubmed publisher
    ..Kidney dysfunction was paralleled by upregulation of ROS generating enzymes such as NOX2, NOX4 and iNOS with concomitant oxidative stress...
  40. Barman S, Chen F, Su Y, Dimitropoulou C, Wang Y, Catravas J, et al. NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to hypertensive vascular remodeling. Arterioscler Thromb Vasc Biol. 2014;34:1704-15 pubmed publisher
    ..Elevated production of reactive oxygen species by NADPH oxidase 4 (Nox4) is associated with increased pressure in PH...
  41. Jung Y, Lee S, Park J, Seo H, Choi B, Shin H. Electroacupuncture preconditioning reduces ROS generation with NOX4 down-regulation and ameliorates blood-brain barrier disruption after ischemic stroke. J Biomed Sci. 2016;23:32 pubmed publisher
    ..The expression of NADPH oxidase 4 (NOX4), not NOX2, was significantly suppressed in EA preconditioned mice...
  42. Murray T, Smyrnias I, Schnelle M, Mistry R, Zhang M, Beretta M, et al. Redox regulation of cardiomyocyte cell cycling via an ERK1/2 and c-Myc-dependent activation of cyclin D2 transcription. J Mol Cell Cardiol. 2015;79:54-68 pubmed publisher
    ..We have generated a transgenic (Tg) mouse model in which the H2O2-generating enzyme, NADPH oxidase 4 (Nox4), is overexpressed within the postnatal cardiomyocytes, and observed that the hearts of 1-3week old Tg ..
  43. Yu B, Liu Z, Fu Y, Wang Y, Zhang L, Cai Z, et al. CYLD Deubiquitinates Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4 Contributing to Adventitial Remodeling. Arterioscler Thromb Vasc Biol. 2017;37:1698-1709 pubmed publisher
    ..whether CYLD mediates AF activation via the regulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) as it is an essential factor during AF transdifferentiation...
  44. Fujii M, Inoguchi T, Maeda Y, Sasaki S, Sawada F, Saito R, et al. Pitavastatin ameliorates albuminuria and renal mesangial expansion by downregulating NOX4 in db/db mice. Kidney Int. 2007;72:473-80 pubmed
    ..ameliorates nephropathy in db/db mice, a rodent model of type 2 diabetes, via downregulation of NAD(P)H oxidase NOX4, which is a major source of oxidative stress in the kidney...
  45. Diebold I, Petry A, Hess J, Gorlach A. The NADPH oxidase subunit NOX4 is a new target gene of the hypoxia-inducible factor-1. Mol Biol Cell. 2010;21:2087-96 pubmed publisher
    ..b>NOX4 appears to be involved in vascular signaling and may contribute to the response to hypoxia...
  46. Bernard K, Logsdon N, Miguel V, Benavides G, Zhang J, Carter A, et al. NADPH Oxidase 4 (Nox4) Suppresses Mitochondrial Biogenesis and Bioenergetics in Lung Fibroblasts via a Nuclear Factor Erythroid-derived 2-like 2 (Nrf2)-dependent Pathway. J Biol Chem. 2017;292:3029-3038 pubmed publisher
    ..The reactive oxygen species-generating enzyme, NADPH oxidase 4 (Nox4), regulates a number of physiological and pathological processes, including cellular differentiation, ..
  47. Rezende F, Schürmann C, Schütz S, Harenkamp S, Herrmann E, Seimetz M, et al. Knock out of the NADPH oxidase Nox4 has no impact on life span in mice. Redox Biol. 2017;11:312-314 pubmed publisher
    ..b>Nox4, a member of the family of NADPH oxidases constitutively produces ROS and therefore has the potential to be a main ..
  48. Wu X, Du L, Xu X. [Relationship between expression of endothelial nitric oxide synthase and NADPH oxidase in lungs of mice exposed to chronic hypoxia]. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17:1001-6 pubmed
    ..Real-time PCR was used to measure the mRNA expression of NOX2, NOX4, and eNOS in mouse lungs...
  49. Weyemi U, Redon C, Aziz T, Choudhuri R, Maeda D, Parekh P, et al. NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease. Proc Natl Acad Sci U S A. 2015;112:2121-6 pubmed publisher
    ..Here, we provide, to our knowledge, the first evidence that NADPH oxidase 4 (NOX4) is involved in manifesting A-T disease...
  50. Lambeth J, Cheng G, Arnold R, Edens W. Novel homologs of gp91phox. Trends Biochem Sci. 2000;25:459-61 pubmed
  51. Harijith A, Pendyala S, Reddy N, Bai T, Usatyuk P, Berdyshev E, et al. Sphingosine kinase 1 deficiency confers protection against hyperoxia-induced bronchopulmonary dysplasia in a murine model: role of S1P signaling and Nox proteins. Am J Pathol. 2013;183:1169-1182 pubmed publisher
    ..attenuated hyperoxia-induced accumulation of IL-6 in bronchoalveolar lavage fluids and NADPH oxidase (NOX) 2 and NOX4 protein expression in lung tissue...
  52. Yang S, Madyastha P, Bingel S, Ries W, Key L. A new superoxide-generating oxidase in murine osteoclasts. J Biol Chem. 2001;276:5452-8 pubmed
    ..This new oxidase complex was present and functional in osteoclasts from p91 knockout mice, explaining the normal resorptive activity seen in the osteoclasts where no p91 is present. ..
  53. Nishimura A, Ago T, Kuroda J, Arimura K, Tachibana M, Nakamura K, et al. Detrimental role of pericyte Nox4 in the acute phase of brain ischemia. J Cereb Blood Flow Metab. 2016;36:1143-54 pubmed publisher
    ..b>Nox4 is a major source of reactive oxygen species in cardiovascular cells and modulate cellular functions, particularly ..
  54. Xiao Q, Luo Z, Pepe A, Margariti A, Zeng L, Xu Q. Embryonic stem cell differentiation into smooth muscle cells is mediated by Nox4-produced H2O2. Am J Physiol Cell Physiol. 2009;296:C711-23 pubmed publisher
    NADPH oxidase (Nox4) produces reactive oxygen species (ROS) that are important for vascular smooth muscle cell (SMC) behavior, but the potential impact of Nox4 in stem cell differentiation is unknown...
  55. Zhang J, Chandrashekar K, Lu Y, Duan Y, Qu P, Wei J, et al. Enhanced expression and activity of Nox2 and Nox4 in the macula densa in ANG II-induced hypertensive mice. Am J Physiol Renal Physiol. 2014;306:F344-50 pubmed publisher
    NAD(P)H oxidase (Nox)2 and Nox4 are the isoforms of Nox expressed in the macula densa (MD). MD-derived superoxide (O??), primarily generated by Nox2, is enhanced by acute ANG II stimulation...
  56. Matsushima S, Kuroda J, Zhai P, Liu T, Ikeda S, Nagarajan N, et al. Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling. J Clin Invest. 2016;126:3403-16 pubmed publisher
    NADPH oxidases (Noxes) produce ROS that regulate cell growth and death. NOX4 expression in cardiomyocytes (CMs) plays an important role in cardiac remodeling and injury, but the posttranslational mechanisms that modulate this enzyme are ..
  57. Li J, Wang J, Zhang S. NADPH oxidase 4-derived H2O2 promotes aberrant retinal neovascularization via activation of VEGF receptor 2 pathway in oxygen-induced retinopathy. J Diabetes Res. 2015;2015:963289 pubmed publisher
    b>NADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidase in retinal endothelial cells. Our previous study suggests that upregulation of Nox4 in retinal endothelial cells contributes to retinal vascular leakage in diabetes...
  58. Liu G, Peshavariya H, Higuchi M, Brewer A, Chang C, Chan E, et al. Microphthalmia-associated transcription factor modulates expression of NADPH oxidase type 4: a negative regulator of melanogenesis. Free Radic Biol Med. 2012;52:1835-43 pubmed publisher
    ..b>NADPH oxidase 4 (Nox4) was found to be the most abundant isoform expressed in B16 cells, and its gene levels, as well as ROS ..
  59. Piwkowska A, Rogacka D, Jankowski M, Angielski S. Metformin reduces NAD(P)H oxidase activity in mouse cultured podocytes through purinergic dependent mechanism by increasing extracellular ATP concentration. Acta Biochim Pol. 2013;60:607-12 pubmed
    ..Metformin, which increases extracellular ATP concentration leads to activation of P2 receptors and consequent modulation of the podocytes' metabolism through AMPK and NAD(P)H oxidase which, in turn, may affect podocyte functioning. ..
  60. Das R, Xu S, Quan X, Nguyen T, Kong I, Chung C, et al. Upregulation of mitochondrial Nox4 mediates TGF-?-induced apoptosis in cultured mouse podocytes. Am J Physiol Renal Physiol. 2014;306:F155-67 pubmed publisher
    ..through caspase-3 activation, which was related to elevated ROS levels generated by selective upregulation of NADPH oxidase 4 (Nox4)...
  61. Ullevig S, Zhao Q, Lee C, Seok Kim H, ZAMORA D, Asmis R. NADPH oxidase 4 mediates monocyte priming and accelerated chemotaxis induced by metabolic stress. Arterioscler Thromb Vasc Biol. 2012;32:415-26 pubmed publisher
    ..of monocytes to diabetic conditions induced by human LDL plus high D-glucose concentrations (LDL+HG) promoted NADPH Oxidase 4 (Nox4) expression, increased intracellular H(2)O(2) formation, stimulated protein S-glutathionylation, and ..
  62. Kassan M, Ait Aissa K, Ali M, Trebak M, Matrougui K. Augmented EGF receptor tyrosine kinase activity impairs vascular function by NADPH oxidase-dependent mechanism in type 2 diabetic mouse. Biochim Biophys Acta. 2015;1853:2404-10 pubmed publisher
    ..function improvement was associated with the rescue of eNOS and Akt and reduction in phosphorylated Rho-kinase, NOX4 mRNA levels, and NADPH oxidase activity...
  63. Ha J, Lee J, Lee J, Lee C, Maeng J, Bae Y, et al. Nox4-dependent H2O2 production contributes to chronic glutamate toxicity in primary cortical neurons. Exp Cell Res. 2010;316:1651-61 pubmed publisher
    ..The Nox4 siRNA reduced NMDA-induced H(2)O(2) production by 54% and cytotoxicity in parallel, suggesting that Nox4-containing ..
  64. Jha J, Thallas Bonke V, Banal C, Gray S, Chow B, Ramm G, et al. Podocyte-specific Nox4 deletion affords renoprotection in a mouse model of diabetic nephropathy. Diabetologia. 2016;59:379-89 pubmed publisher
    ..b>NADPH oxidase 4 (NOX4) is the main source of reactive oxygen species (ROS) in the kidney and Nox4 is upregulated in podocytes ..
  65. Hong N, Garvin J. NADPH oxidase 4 mediates flow-induced superoxide production in thick ascending limbs. Am J Physiol Renal Physiol. 2012;303:F1151-6 pubmed publisher
    ..Of the three isoforms expressed in the kidney-Nox1, Nox2, and Nox4-we hypothesized that Nox4 is responsible for flow-induced O(2)(-) production in TALs...
  66. Rashdan N, Lloyd P. Fluid shear stress upregulates placental growth factor in the vessel wall via NADPH oxidase 4. Am J Physiol Heart Circ Physiol. 2015;309:H1655-66 pubmed publisher
    ..Further studies identified NADPH oxidase 4 as a source of reactive oxygen species for this pathway...
  67. Anea C, Zhang M, Chen F, Ali M, Hart C, Stepp D, et al. Circadian clock control of Nox4 and reactive oxygen species in the vasculature. PLoS ONE. 2013;8:e78626 pubmed publisher
    ..The goal in the current study was to determine if the circadian clock controls vascular Nox4 expression and hydrogen peroxide formation in arteries, particularly in endothelial and vascular smooth muscle ..
  68. Yu L, Liu Y, Wu Y, Liu Q, Feng J, Gu X, et al. Smad3/Nox4-mediated mitochondrial dysfunction plays a crucial role in puromycin aminonucleoside-induced podocyte damage. Cell Signal. 2014;26:2979-91 pubmed publisher
    ..Furthermore, an obvious translocation of p-Smad3 from the cytosol to nuclei and induction of mitochondrial Nox4 were detected following PA application...
  69. Matsushima S, Kuroda J, Ago T, Zhai P, Ikeda Y, Oka S, et al. Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1? and upregulation of peroxisome proliferator-activated receptor-?. Circ Res. 2013;112:1135-49 pubmed publisher
    NADPH oxidase (Nox) 2 and Nox4 are major components of the Nox family which purposefully produce reactive oxidative species, namely O2(-) and H2O2, in the heart...
  70. Di Marco E, Gray S, Chew P, Kennedy K, Cooper M, Schmidt H, et al. Differential effects of NOX4 and NOX1 on immune cell-mediated inflammation in the aortic sinus of diabetic ApoE-/- mice. Clin Sci (Lond). 2016;130:1363-74 pubmed publisher
    ..In the present study we investigated the roles of the NADPH oxidase subunit isoforms, NOX4 and NOX1, in immune cell activation and recruitment to the aortic sinus atherosclerotic plaque in diabetic ApoE(-/-)..
  71. Rueckschloss U, Villmow M, Klockner U. NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes. Exp Gerontol. 2010;45:788-96 pubmed publisher
    ..In summary, we show that increased superoxide formation by upregulated NADPH oxidase contributes significantly to age-dependent alterations in calcium handling and contractility of murine ventricular myocytes. ..
  72. Pietrowski E, Bender B, Huppert J, White R, Luhmann H, Kuhlmann C. Pro-inflammatory effects of interleukin-17A on vascular smooth muscle cells involve NAD(P)H- oxidase derived reactive oxygen species. J Vasc Res. 2011;48:52-8 pubmed publisher
    ..Taken together, our data indicate that IL-17A causes the NAD(P)H-oxidase dependent generation of ROS leading to a pro-inflammatory activation of VSMC. ..
  73. Palumbo S, Shin Y, Ahmad K, Desai A, Quijada H, Mohamed M, et al. Dysregulated Nox4 ubiquitination contributes to redox imbalance and age-related severity of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2017;312:L297-L308 pubmed publisher
    ..of reactive oxygen species (ROS) in the BAL, which was associated with upregulation of the ROS-generating enzyme, Nox4. We evaluated the role of aging in human lung EC barrier regulation utilizing a cellular model of replicative ..
  74. Matsushima S, Kuroda J, Ago T, Zhai P, Park J, Xie L, et al. Increased oxidative stress in the nucleus caused by Nox4 mediates oxidation of HDAC4 and cardiac hypertrophy. Circ Res. 2013;112:651-63 pubmed publisher
    ..We investigated whether nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4), a major nicotinamide adenine dinucleotide phosphate oxidase, mediates cysteine oxidation of HDAC4...
  75. Ghatak S, Hascall V, Markwald R, Feghali Bostwick C, Artlett C, Gooz M, et al. Transforming growth factor ?1 (TGF?1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis. J Biol Chem. 2017;292:10490-10519 pubmed publisher
    ..b>NADPH oxidase 4 (NOX4) enzyme, which catalyzes the reduction of O2 to hydrogen peroxide (H2O2..
  76. Case A, Li S, Basu U, Tian J, Zimmerman M. Mitochondrial-localized NADPH oxidase 4 is a source of superoxide in angiotensin II-stimulated neurons. Am J Physiol Heart Circ Physiol. 2013;305:H19-28 pubmed publisher
    ..b>NADPH oxidase 4 (Nox4), a member of the NADPH oxidase family, has been reported to be localized in mitochondria of various ..
  77. Sato N, Takasaka N, Yoshida M, Tsubouchi K, Minagawa S, Araya J, et al. Metformin attenuates lung fibrosis development via NOX4 suppression. Respir Res. 2016;17:107 pubmed publisher
    ..Metformin-mediated activation of AMPK was responsible for inhibiting TGF-?-induced NOX4 expression...
  78. Hirschhäuser C, Bornbaum J, Reis A, Böhme S, Kaludercic N, Menabò R, et al. NOX4 in Mitochondria: Yeast Two-Hybrid-Based Interaction with Complex I Without Relevance for Basal Reactive Oxygen Species?. Antioxid Redox Signal. 2015;23:1106-12 pubmed publisher
    ..The aim of this study was to identify NOX4-binding proteins and examine the possible physiological localization of NOX4 to mitochondria and its impact on ..
  79. Sedwick C. NOX4: a guilty party in stroke damage. PLoS Biol. 2010;8: pubmed publisher