Gene Symbol: Nox4
Description: NADPH oxidase 4
Alias: NADPH oxidase 4, kidney oxidase-1, kidney superoxide-producing NADPH oxidase, kox-1
Species: rat
Products:     Nox4

Top Publications

  1. Gorin Y, Ricono J, Kim N, Bhandari B, Choudhury G, Abboud H. Nox4 mediates angiotensin II-induced activation of Akt/protein kinase B in mesangial cells. Am J Physiol Renal Physiol. 2003;285:F219-29 pubmed
    ..explored the role of the small GTPase Rac1, a component of the phagocyte NADPH oxidase, and the gp91phox homologue Nox4/Renox in this signaling pathway...
  2. Maalouf R, Eid A, Gorin Y, Block K, Escobar G, Bailey S, et al. Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes. Am J Physiol Cell Physiol. 2012;302:C597-604 pubmed publisher
    Oxidative stress contributes to diabetic cardiomyopathy. This study explored the role of the NADPH oxidase Nox4 as a source of reactive oxygen species (ROS) involved in the development of diabetic cardiomyopathy...
  3. Ambasta R, Kumar P, Griendling K, Schmidt H, Busse R, Brandes R. Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase. J Biol Chem. 2004;279:45935-41 pubmed
    Nox1 and Nox4, homologues of the leukocyte NADPH oxidase subunit Nox2 (gp91phox) mediate superoxide anion formation in various cell types. However, their interactions with other components of the NADPH oxidase are poorly defined...
  4. Meng D, Lv D, Fang J. Insulin-like growth factor-I induces reactive oxygen species production and cell migration through Nox4 and Rac1 in vascular smooth muscle cells. Cardiovasc Res. 2008;80:299-308 pubmed publisher
    ..Inhibition of NADPH oxidase 4 (Nox4) or Rac1 was performed by means of siRNA technology...
  5. 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...
  6. Wang Z, Wei X, Zhang Y, Ma X, Li B, Zhang S, et al. NADPH oxidase-derived ROS contributes to upregulation of TRPC6 expression in puromycin aminonucleoside-induced podocyte injury. Cell Physiol Biochem. 2009;24:619-26 pubmed publisher
    ..Podocyte effacement, NADPH oxidase subunit NOX4 expression, enzyme activity and TRPC6 expression were significant increased in glomeruli from PAN nephrosis rats...
  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. Nisbet R, Graves A, Kleinhenz D, Rupnow H, Reed A, Fan T, et al. The role of NADPH oxidase in chronic intermittent hypoxia-induced pulmonary hypertension in mice. Am J Respir Cell Mol Biol. 2009;40:601-9 pubmed publisher
    ..CIH-induced pulmonary hypertension was associated with increased lung levels of the NADPH oxidase subunits, Nox4 and p22phox, as well as increased activity of platelet-derived growth factor receptor beta and its associated ..
  9. Clempus R, Sorescu D, Dikalova A, Pounkova L, Jo P, Sorescu G, et al. Nox4 is required for maintenance of the differentiated vascular smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol. 2007;27:42-8 pubmed
    ..In this study, we investigated the role of Nox1 and Nox4-derived ROS in this process...

More Information


  1. Tang R, Zhou Q, Ao X, Peng W, Veeraragoo P, Tang T. Fosinopril and losartan regulate klotho gene and nicotinamide adenine dinucleotide phosphate oxidase expression in kidneys of spontaneously hypertensive rats. Kidney Blood Press Res. 2011;34:350-7 pubmed publisher
    ..Fos and Los can increase Klotho expression, and inhibit NADPH oxidase expression, which may be one of the mechanisms of their protective effects in hypertensive renal damage. ..
  2. Lyle A, Deshpande N, Taniyama Y, Seidel Rogol B, Pounkova L, Du P, et al. Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth muscle cells. Circ Res. 2009;105:249-59 pubmed publisher
    ..novel p22phox binding partner, Poldip2, and demonstrated that it associates with p22phox, NADPH oxidase (Nox)1, and Nox4 and colocalizes with p22phox at sites of Nox4 localization...
  3. Carmona Cuenca I, Roncero C, Sancho P, Caja L, Fausto N, Fernandez M, et al. Upregulation of the NADPH oxidase NOX4 by TGF-beta in hepatocytes is required for its pro-apoptotic activity. J Hepatol. 2008;49:965-76 pubmed publisher
    ..TGF-beta upregulates the Rac-independent Nox4, which correlates with its pro-apoptotic activity...
  4. Zheng D, Dong S, Li T, Yang F, Yu X, Wu J, et al. Exogenous Hydrogen Sulfide Attenuates Cardiac Fibrosis Through Reactive Oxygen Species Signal Pathways in Experimental Diabetes Mellitus Models. Cell Physiol Biochem. 2015;36:917-29 pubmed publisher
    ..We tested the effects of GYY4137 (a slow-releasing H2S donor), NaHS (an exogenous H2S donor) and NADPH oxidase 4 (NOX4) siRNA on reactive oxygen species (ROS) production, MMP-2,9, cystathionine-γ-lyase (CSE), NOX4, and ..
  5. Tong X, Hou X, JOURD HEUIL D, Weisbrod R, Cohen R. Upregulation of Nox4 by TGF{beta}1 oxidizes SERCA and inhibits NO in arterial smooth muscle of the prediabetic Zucker rat. Circ Res. 2010;107:975-83 pubmed publisher
    ..In culture, ZO aortic SMCs showed a significant increase in Nox4 mRNA and protein levels compared with the control lean Zucker rat (ZL)...
  6. He L, Liu X, Chen J, Dinger B, Stensaas L, Fidone S. Modulation of chronic hypoxia-induced chemoreceptor hypersensitivity by NADPH oxidase subunits in rat carotid body. J Appl Physiol (1985). 2010;108:1304-10 pubmed publisher
    ..5-fold) and NOX4 (approximately 3.8-fold) and also increased presence of the regulatory subunit p47phox (approximately 4.2-fold)...
  7. Zhang X, Cao X, Zhang C, Zhao Z. 17β-estradiol protects against doxorubicin-induced cardiotoxicity in male Sprague-Dawley rats by regulating NADPH oxidase and apoptosis genes. Mol Med Rep. 2017;15:2695-2702 pubmed publisher
    ..increase in the expression of cardiac genes, nicotinamide adenine dinucleotide phosphate oxidase (NOX) 2, NOX4, B‑cell lymphoma 2‑associated X protein and caspase 3...
  8. Wang P, Tang F, Li R, Zhang H, Chen S, Liu P, et al. Contribution of different Nox homologues to cardiac remodeling in two-kidney two-clip renovascular hypertensive rats: effect of valsartan. Pharmacol Res. 2007;55:408-17 pubmed
    ..Nox2 and Nox4 protein expression increased in heart, while Nox1 and Nox4 increased in aorta in 2K2C hypertensive rats, which were ..
  9. Fortunato R, Braga W, Ortenzi V, Rodrigues D, Andrade B, Miranda Alves L, et al. Sexual dimorphism of thyroid reactive oxygen species production due to higher NADPH oxidase 4 expression in female thyroid glands. Thyroid. 2013;23:111-9 pubmed publisher
    ..oxidases (NOX) involved in hydrogen peroxide production necessary for thyroid hormonogenesis, but recently, the NOX4 has also been described in the thyroid gland...
  10. Gojo A, Utsunomiya K, Taniguchi K, Yokota T, Ishizawa S, Kanazawa Y, et al. The Rho-kinase inhibitor, fasudil, attenuates diabetic nephropathy in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2007;568:242-7 pubmed
    ..Expression of NOX4 mRNA (catalytic subunit of NAD(P)H oxidase) was up-regulated in the renal cortex of diabetic rats, an effect which ..
  11. Qiao X, Wang L, Wang Y, Su X, Qi Y, Fan Y, et al. Intermedin inhibits unilateral ureteral obstruction-induced oxidative stress via NADPH oxidase Nox4 and cAMP-dependent mechanisms. Ren Fail. 2017;39:652-659 pubmed publisher
    NADPH oxidase Nox4-derived reactive oxygen species (ROS) play important roles in renal fibrosis...
  12. Sharma K, Ramachandrarao S, Qiu G, Usui H, Zhu Y, Dunn S, et al. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest. 2008;118:1645-56 pubmed publisher
    ..reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes...
  13. Gorin Y, Block K, Hernandez J, Bhandari B, Wagner B, Barnes J, et al. Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. J Biol Chem. 2005;280:39616-26 pubmed
    ..We investigated the role of the NAD(P)H oxidase Nox4 in generation of reactive oxygen species (ROS), hypertrophy, and fibronectin expression in a rat model of type 1 ..
  14. 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
  15. Gil Lorenzo A, Costantino V, Appiolaza M, Cacciamani V, Benardon M, Bocanegra V, et al. Heat Shock Protein 70 and CHIP Promote Nox4 Ubiquitination and Degradation within the Losartan Antioxidative Effect in Proximal Tubule Cells. Cell Physiol Biochem. 2015;36:2183-97 pubmed publisher
    ..We study whether Hsp70/CHIP contribute to the negative regulation of Nox4 after AT1R blockage...
  16. Sancho P, Bertran E, Caja L, Carmona Cuenca I, Murillo M, Fabregat I. The inhibition of the epidermal growth factor (EGF) pathway enhances TGF-beta-induced apoptosis in rat hepatoma cells through inducing oxidative stress coincident with a change in the expression pattern of the NADPH oxidases (NOX) isoforms. Biochim Biophys Acta. 2009;1793:253-63 pubmed publisher
    ..However, the treatment with TGF-beta and AG1478 greatly enhanced the expression of another family member: nox4. NOX1 and NOX4 targeted knock-down by siRNA experiments suggest that they play opposite roles, because NOX1 ..
  17. Ding R, Jiang H, Sun B, Wu X, Li W, Zhu S, et al. Advanced oxidation protein products sensitized the transient receptor potential vanilloid 1 via NADPH oxidase 1 and 4 to cause mechanical hyperalgesia. Redox Biol. 2016;10:1-11 pubmed publisher
    ..Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1), NADPH oxidase 4 (Nox4), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in the ..
  18. Zhan R, Xu K, Pan J, Xu Q, Xu S, Shen J. Long noncoding RNA MEG3 mediated angiogenesis after cerebral infarction through regulating p53/NOX4 axis. Biochem Biophys Res Commun. 2017;490:700-706 pubmed publisher
    ..RIP) assay was used to detect the interaction between MEG3 and p53, and the relationship between p53 and NOX4 was proved by chromatin co-immunoprecipitation (chip) assay...
  19. Anilkumar N, San José G, Sawyer I, Santos C, Sand C, Brewer A, et al. A 28-kDa splice variant of NADPH oxidase-4 is nuclear-localized and involved in redox signaling in vascular cells. Arterioscler Thromb Vasc Biol. 2013;33:e104-12 pubmed publisher
    ..b>Nox4 is unique among Noxs in being constitutively active, and its subcellular localization may therefore be particularly ..
  20. Lassegue B, Sorescu D, Szocs K, Yin Q, Akers M, Zhang Y, et al. Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res. 2001;88:888-94 pubmed
    ..In this study, we examined the expression of three nox family members, nox1, nox4, and gp91(phox), in VSMCs, their regulation by angiotensin II (Ang II), and their role in redox-sensitive signaling...
  21. Lee J, Cho K, Lee K, Kim J, Bae Y. Nox4-mediated cell signaling regulates differentiation and survival of neural crest stem cells. Mol Cells. 2014;37:907-11 pubmed publisher
    ..Among the ROS-generating Nox isozymes, only Nox4 was expressed at a detectable level in NCSCs...
  22. Dikalov S, Dikalova A, Bikineyeva A, Schmidt H, Harrison D, Griendling K. Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. Free Radic Biol Med. 2008;45:1340-51 pubmed publisher
    ..It is known that the heme-containing catalytic subunits Nox1 and Nox4 are responsible for oxygen reduction in vascular smooth muscle cells from large arteries...
  23. Gao S, Yuan K, Shah A, Kim J, Park W, Kim S. Suppression of high pacing-induced ANP secretion by antioxidants in isolated rat atria. Peptides. 2011;32:2467-73 pubmed publisher
    ..These results suggest that intracellular ROS formation partly through an increasing NOX activity in response to high pacing frequency is associated with an increased ANP secretion in rat atria. ..
  24. Bocanegra V, Manucha W, Peña M, Cacciamani V, Valles P. Caveolin-1 and Hsp70 interaction in microdissected proximal tubules from spontaneously hypertensive rats as an effect of Losartan. J Hypertens. 2010;28:143-55 pubmed publisher
    ..01) was reversed by the preincubation with anti-Hsp70 antibody. In addition, interaction between Hsp70 and Nox4 was determined by the coimmunoprecipitation strategy showing that membrane overexpression of Hsp70 was associated ..
  25. Cutz E, Pan J, Yeger H. The role of NOX2 and "novel oxidases" in airway chemoreceptor O(2) sensing. Adv Exp Med Biol. 2009;648:427-38 pubmed publisher
    ..2, 1.5, 2.1, 3.1, 3.3, 3.4, 4.2, 4.3;TASK1-3). In rat lung, NOX2, NOX4, p22phox, Kv3.3 (and Kv3...
  26. Piwkowska A, Rogacka D, Audzeyenka I, Angielski S, Jankowski M. High glucose increases glomerular filtration barrier permeability by activating protein kinase G type I? subunits in a Nox4-dependent manner. Exp Cell Res. 2014;320:144-52 pubmed publisher
    ..It was also abolished by introducing small interfering RNAs (siRNAs) against Nox4 and PKGI? into cultured podocytes. Furthermore, HG increased PKGI? dimerization by 138% (0.23 ± 0.04 vs. 0.54 ± 0...
  27. Haurani M, Cifuentes M, Shepard A, Pagano P. Nox4 oxidase overexpression specifically decreases endogenous Nox4 mRNA and inhibits angiotensin II-induced adventitial myofibroblast migration. Hypertension. 2008;52:143-9 pubmed publisher
    ..migration in vitro via reduced nicotinamide-adenine dinucleotide phosphate oxidase-derived H(2)O(2) and that Nox4-based oxidase promotes migration...
  28. Massey K, Hong N, Garvin J. Angiotensin II stimulates superoxide production in the thick ascending limb by activating NOX4. Am J Physiol Cell Physiol. 2012;303:C781-9 pubmed publisher
    ..6 WT vs. KO). To test whether NOX4 mediates the effect of ANG II, we selectively decreased NOX4 expression in rats using an adenovirus that expresses ..
  29. Zeng S, Chen X, Chen S, Li Q, Wang Y, Zou J, et al. Upregulation of Nox4 promotes angiotensin II-induced epidermal growth factor receptor activation and subsequent cardiac hypertrophy by increasing ADAM17 expression. Can J Cardiol. 2013;29:1310-9 pubmed publisher
    ..In this study, we aimed to confirm the important role of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) in Ang II-induced EGFR activation and subsequent cardiac hypertrophy by upregulating expression of a disintegrin ..
  30. Block K, Eid A, Griendling K, Lee D, Wittrant Y, Gorin Y. Nox4 NAD(P)H oxidase mediates Src-dependent tyrosine phosphorylation of PDK-1 in response to angiotensin II: role in mesangial cell hypertrophy and fibronectin expression. J Biol Chem. 2008;283:24061-76 pubmed publisher
    ..Ang II also up-regulates Nox4 protein, and siNox4 abrogates the Ang II-induced increase in intracellular reactive oxygen species (ROS) generation...
  31. New D, Block K, Bhandhari B, Gorin Y, Abboud H. IGF-I increases the expression of fibronectin by Nox4-dependent Akt phosphorylation in renal tubular epithelial cells. Am J Physiol Cell Physiol. 2012;302:C122-30 pubmed publisher
    ..superoxide generation, enhances the release of hydrogen peroxide, and increases the expression of NADPH oxidase 4 (Nox4) in PTCs...
  32. 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 ..
  33. Ginnan R, Jourd heuil F, Guikema B, Simons M, Singer H, JOURD HEUIL D. NADPH oxidase 4 is required for interleukin-1β-mediated activation of protein kinase Cδ and downstream activation of c-jun N-terminal kinase signaling in smooth muscle. Free Radic Biol Med. 2013;54:125-34 pubmed publisher
    ..In this study, we tested the hypothesis that NOX4 is a proximal mediator of IL-1β-dependent activation of PKCδ and increases IL-1β-stimulated c-Jun kinase (..
  34. Zhang R, Harding P, Garvin J, Juncos R, Peterson E, Juncos L, et al. Isoforms and functions of NAD(P)H oxidase at the macula densa. Hypertension. 2009;53:556-63 pubmed publisher
    ..The captured cells expressed neuronal NOS (marker of macula densa), NOX2, and NOX4 but not NOX1. Expression of the NOXs and neuronal NOS was essentially identical in the MMDD1 cells...
  35. Lu G, Xu C, Tang K, Zhang J, Li Q, Peng L, et al. H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation. Biochem Biophys Res Commun. 2017;483:534-540 pubmed publisher
    ..that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart...
  36. 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...
  37. 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...
  38. Manickam N, Patel M, Griendling K, Gorin Y, Barnes J. RhoA/Rho kinase mediates TGF-?1-induced kidney myofibroblast activation through Poldip2/Nox4-derived reactive oxygen species. Am J Physiol Renal Physiol. 2014;307:F159-71 pubmed publisher
    ..Recent studies in our laboratory have shown that NADPH oxidase Nox4-derived ROS are involved in transforming growth factor (TGF)-?1-induced rat kidney myofibroblast differentiation ..
  39. Collins Underwood J, Zhao W, Sharpe J, Robbins M. NADPH oxidase mediates radiation-induced oxidative stress in rat brain microvascular endothelial cells. Free Radic Biol Med. 2008;45:929-38 pubmed publisher
    ..ii) activation of the transcription factor NFkappaB, (iii) expression of ICAM-1 and PAI-1, and (iv) expression of Nox4, p22(phox), and p47(phox)...
  40. Akasaki T, Ohya Y, Kuroda J, Eto K, Abe I, Sumimoto H, et al. Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: involvement of the renin-angiotensin system. Hypertens Res. 2006;29:813-20 pubmed
    ..of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic ..
  41. Harrigan T, Abdullaev I, JOURD HEUIL D, Mongin A. Activation of microglia with zymosan promotes excitatory amino acid release via volume-regulated anion channels: the role of NADPH oxidases. J Neurochem. 2008;106:2449-62 pubmed publisher
    ..This pharmacologic profile pointed to the potential involvement of apocynin-insensitive NOX4. Using RT-PCR we confirmed that NOX4 is expressed in rat microglial cells along with NOX1 and NOX2...
  42. Hilenski L, Clempus R, Quinn M, Lambeth J, Griendling K. Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2004;24:677-83 pubmed
    ..Nox1 and Nox4, two homologues to the phagocytic NAD(P)H subunit gp91phox, both generate ROS in VSMC but differ in their response ..
  43. Chignalia A, Schuldt E, Camargo L, Montezano A, Callera G, Laurindo F, et al. Testosterone induces vascular smooth muscle cell migration by NADPH oxidase and c-Src-dependent pathways. Hypertension. 2012;59:1263-71 pubmed publisher
    ..Testosterone increased Nox1 and Nox4 mRNA levels and p47phox protein expression, determined by real-time PCR and immunoblotting, respectively...
  44. Qi W, Niu J, Qin Q, Qiao Z, Gu Y. Glycated albumin triggers fibrosis and apoptosis via an NADPH oxidase/Nox4-MAPK pathway-dependent mechanism in renal proximal tubular cells. Mol Cell Endocrinol. 2015;405:74-83 pubmed publisher
    ..Real-time PCR showed that GA increased Nox1, Nox2 and Nox4 mRNA expressions, especially the Nox4 expression...
  45. Wang C, Li J, Lv X, Zhang M, Song Y, Chen L, et al. Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur J Pharmacol. 2009;620:131-7 pubmed publisher
    ..nitric oxide synthase (eNOS) mRNA was measured by RT-PCR, and the protein expressions of eNOS and NADPH oxidase (NOX4) were analyzed by western blot...
  46. Tada Y, Kitazato K, Tamura T, Yagi K, Shimada K, Kinouchi T, et al. Role of mineralocorticoid receptor on experimental cerebral aneurysms in rats. Hypertension. 2009;54:552-7 pubmed publisher
    ..The mRNA levels of Ang-converting enzyme 1 and NADPH oxidase subunits NOX4, Rac1, monocyte chemoattractant protein 1, and matrix metalloproteinase 9 were increased...
  47. Zhang L, Li Z, Feng D, Shen H, Tian X, Li H, et al. Involvement of Nox2 and Nox4 NADPH oxidases in early brain injury after subarachnoid hemorrhage. Free Radic Res. 2017;51:316-328 pubmed publisher
    ..Nox2 has been shown to participate in SAH-induced early brain injury (EBI). Nox4 is another major subtype of Nox family widely expressed in central nervous system (CNS)...
  48. Wang J, Hong Z, Zeng C, Yu Q, Wang H. NADPH oxidase 4 promotes cardiac microvascular angiogenesis after hypoxia/reoxygenation in vitro. Free Radic Biol Med. 2014;69:278-88 pubmed publisher
    ..However, the roles of the various ROS sources remain unclear. This study sought to investigate the role of NADPH oxidase 4 (Nox4) in the cardiac microvascular endothelium in response to I/R injury...
  49. Lin C, Lee S, Huang H, Chen Y, Ma M. H2O2 generated by NADPH oxidase 4 contributes to transient receptor potential vanilloid 1 channel-mediated mechanosensation in the rat kidney. Am J Physiol Renal Physiol. 2015;309:F369-76 pubmed publisher
    The presence of NADPH oxidase (Nox) in the kidney, especially Nox4, results in H2O2 production, which regulates Na(+) excretion and urine formation...
  50. Zheleznova N, Yang C, Cowley A. Role of Nox4 and p67phox subunit of Nox2 in ROS production in response to increased tubular flow in the mTAL of Dahl salt-sensitive rats. Am J Physiol Renal Physiol. 2016;311:F450-8 pubmed publisher
    b>Nox4 and Nox2 are the most abundant NADPH oxidases (Nox) in the kidney and have been shown to contribute to hypertension, renal oxidative stress, and injury in Dahl salt-sensitive (SS) hypertensive rats...
  51. Loureiro A, do Rêgo Monteiro I, Louzada R, Ortenzi V, de Aguiar A, de Abreu E, et al. Differential Expression of NADPH Oxidases Depends on Skeletal Muscle Fiber Type in Rats. Oxid Med Cell Longev. 2016;2016:6738701 pubmed
    ..SOL showed higher NOX activity, as well as NOX2 and NOX4 mRNA levels, antioxidant enzymatic activities, and reactive protein thiol contents when compared to WG and RG...
  52. Meng D, Mei A, Liu J, Kang X, Shi X, Qian R, et al. NADPH oxidase 4 mediates insulin-stimulated HIF-1? and VEGF expression, and angiogenesis in vitro. PLoS ONE. 2012;7:e48393 pubmed publisher
    ..In this study we examined the role of NADPH oxidase subunit 4 (Nox4) in insulin-stimulated HIF-1? and VEGF expression, and angiogenic responses in human microvascular endothelial ..
  53. He J, Li X, Luo H, Li T, Zhao L, Qi Q, et al. Galectin-3 mediates the pulmonary arterial hypertension-induced right ventricular remodeling through interacting with NADPH oxidase 4. J Am Soc Hypertens. 2017;11:275-289.e2 pubmed publisher
    ..Our results showed that the serum Gal-3 and NADPH oxidase 4 (Nox4) levels were significantly elevated and correlated in 26 human PAH patients when compared with 14 age- ..
  54. Shiose A, Kuroda J, Tsuruya K, Hirai M, Hirakata H, Naito S, et al. A novel superoxide-producing NAD(P)H oxidase in kidney. J Biol Chem. 2001;276:1417-23 pubmed
    ..Here we describe the cloning of human cDNA that encodes a novel NAD(P)H oxidase, designated NOX4. The NOX4 protein of 578 amino acids exhibits 39% identity to gp91(phox) with special conservation in membrane-..
  55. Liu B, Ren K, Peng J, Li T, Luo X, Fan C, et al. Suppression of NADPH oxidase attenuates hypoxia-induced dysfunctions of endothelial progenitor cells. Biochem Biophys Res Commun. 2017;482:1080-1087 pubmed publisher
    ..of EPCs (the reduced abilities in adhesion, migration and tube formation), as well as an increase in NOX2 and NOX4 expression, NOX activity and H2O2 production, these phenomena were attenuated by NOX ..
  56. 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. ..
  57. Wagner B, Ricono J, Gorin Y, Block K, Arar M, Riley D, et al. Mitogenic signaling via platelet-derived growth factor beta in metanephric mesenchymal cells. J Am Soc Nephrol. 2007;18:2903-11 pubmed
    ..Using antisense oligonucleotides and small interfering RNA, we determined that the NAD(P)H oxidase Nox4 produces these ROS that activate Akt and the MEK-ERK1/2 mitogenic cascade...
  58. Saha S, Li Y, Anand Srivastava M. Reduced levels of cyclic AMP contribute to the enhanced oxidative stress in vascular smooth muscle cells from spontaneously hypertensive rats. Can J Physiol Pharmacol. 2008;86:190-8 pubmed publisher
    ..In addition, the levels of p47(phox) and Nox4 proteins, subunits of NADPH oxidase, were significantly augmented about 35%-40% in VSMC from SHR compared with ..
  59. Ribaldo P, Souza D, Biswas S, Block K, Lopes de Faria J, Lopes de Faria J. Green tea (Camellia sinensis) attenuates nephropathy by downregulating Nox4 NADPH oxidase in diabetic spontaneously hypertensive rats. J Nutr. 2009;139:96-100 pubmed publisher
    ..and nitrotyrosine expression, NADPH oxidase-dependent superoxide generation, and the expression of renal cortex Nox4 were greater (P < 0...
  60. Janiszewski M, Lopes L, Carmo A, Pedro M, Brandes R, Santos C, et al. Regulation of NAD(P)H oxidase by associated protein disulfide isomerase in vascular smooth muscle cells. J Biol Chem. 2005;280:40813-9 pubmed
    ..Confocal microscopy showed co-localization between PDI and the oxidase subunits p22(phox), Nox1, and Nox4. Co-immunoprecipitation assays supported spatial association between PDI and oxidase subunits p22(phox), Nox1, and ..
  61. Coucha M, Abdelsaid M, Li W, Johnson M, Orfi L, El Remessy A, et al. Nox4 contributes to the hypoxia-mediated regulation of actin cytoskeleton in cerebrovascular smooth muscle. Life Sci. 2016;163:46-54 pubmed publisher
    ..To determine the role of Nox4 in hypoxia-mediated actin depolymerization and myogenic-tone impairment in cerebral vascular smooth muscle...
  62. Varga Z, Kupai K, Szucs G, Gáspár R, Pálóczi J, Faragó N, et al. MicroRNA-25-dependent up-regulation of NADPH oxidase 4 (NOX4) mediates hypercholesterolemia-induced oxidative/nitrative stress and subsequent dysfunction in the heart. J Mol Cell Cardiol. 2013;62:111-21 pubmed publisher
    ..In silico target prediction revealed NADPH oxidase 4 (NOX4) as a putative target of microRNA-25...
  63. Zhang L, Sheppard O, Shah A, Brewer A. Positive regulation of the NADPH oxidase NOX4 promoter in vascular smooth muscle cells by E2F. Free Radic Biol Med. 2008;45:679-85 pubmed publisher
    ..Unlike other members of this family, NOX4 generates ROS constitutively without the need for a stimulus...
  64. Wang R, Dashwood W, Nian H, LOHR C, Fischer K, Tsuchiya N, et al. NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Int J Cancer. 2011;128:2581-90 pubmed publisher
    ..In the PhIP-induced colon tumors obtained after 1 year, Nox1, Nox4, NF?B-p50 and NF?B-p65 were all highly overexpressed compared with their levels in adjacent normal-looking colonic ..
  65. Fu Y, Zhang Y, Wang Z, Wang L, Wei X, Zhang B, et al. Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy. Am J Nephrol. 2010;32:581-9 pubmed publisher
    ..Therefore, the present study was to test whether miRNAs importantly contribute to the regulation of NOX4 expression, a major catalytic subunit of NADPH oxidase under hyperglycemia...
  66. Briones A, Tabet F, Callera G, Montezano A, Yogi A, He Y, et al. Differential regulation of Nox1, Nox2 and Nox4 in vascular smooth muscle cells from WKY and SHR. J Am Soc Hypertens. 2011;5:137-53 pubmed publisher
    ..Expression of Nox1, Nox2, and Nox4 (gene and protein) and NAD(P)H oxidase activity were increased in SHR...
  67. Guo Z, Zhang R, Li J, Xu G. Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats. Cardiovasc Diabetol. 2012;11:94 pubmed publisher
    ..Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4), monocyte chemoattractant protein-1(MCP-1) and connective tissue growth factor (CTGF)..
  68. 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...
  69. Fujii M, Inoguchi T, Sasaki S, Maeda Y, Zheng J, Kobayashi K, et al. Bilirubin and biliverdin protect rodents against diabetic nephropathy by downregulating NAD(P)H oxidase. Kidney Int. 2010;78:905-19 pubmed publisher
    ..Collectively, our findings suggest that BIL and BVD may protect against diabetic nephropathy and may lead to novel antioxidant therapies for diabetic nephropathy. ..
  70. Bondi C, Manickam N, Lee D, Block K, Gorin Y, Abboud H, et al. NAD(P)H oxidase mediates TGF-beta1-induced activation of kidney myofibroblasts. J Am Soc Nephrol. 2010;21:93-102 pubmed publisher
    ..In addition, TGF-beta1 increased both the activity of NADPH oxidase and expression of Nox2 and Nox4, homologs of the NAD(P)H oxidase family, indicating that this growth factor induces production of ROS...
  71. Block K, Gorin Y, Abboud H. Subcellular localization of Nox4 and regulation in diabetes. Proc Natl Acad Sci U S A. 2009;106:14385-90 pubmed publisher
    ..NAD(P)H oxidases have been identified not only in phagocytic but also in somatic cells. Nox4 is the most ubiquitous of these oxidases and is a major source of reactive oxygen species (ROS) in many cell types ..
  72. Liu X, Zhang Q, Pan L, Liu S, Xu P, Luo X, et al. NADPH oxidase 4 contributes to connective tissue growth factor expression through Smad3-dependent signaling pathway. Free Radic Biol Med. 2016;94:174-84 pubmed publisher
    ..In present study, we demonstrated TGF-β1 strongly induced CTGF expression, Smad3 activation, NADPH oxidase 4 (Nox4) expression and increased ROS production in primary rat VSMC in vitro...
  73. Zhou B, Mu J, Gong Y, Lu C, Zhao Y, He T, et al. Brd4 inhibition attenuates unilateral ureteral obstruction-induced fibrosis by blocking TGF-?-mediated Nox4 expression. Redox Biol. 2017;11:390-402 pubmed publisher
    ..Brd4 inhibition also suppressed the oxidative stress induced by UUO in vivo or by TGF-?1 in HK-2 cells. Moreover, Nox4, which is constitutively active in renal cells and is involved in the generation of hydrogen peroxide, was up-..
  74. Wilkinson Berka J, Tan G, Jaworski K, Miller A. Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology. Circ Res. 2009;104:124-33 pubmed publisher
    ..OIR, aldosterone reduced G6PD mRNA, and in late OIR, aldosterone increased mRNA for the NAD(P)H oxidase subunit Nox4. A functional retinal MR-aldosterone system was evident with MR expression, translocation of nuclear MR, and ..
  75. Lee D, Wauquier F, Eid A, Roman L, Ghosh Choudhury G, Khazim K, et al. Nox4 NADPH oxidase mediates peroxynitrite-dependent uncoupling of endothelial nitric-oxide synthase and fibronectin expression in response to angiotensin II: role of mitochondrial reactive oxygen species. J Biol Chem. 2013;288:28668-86 pubmed publisher
    ..Ang II rapidly up-regulates Nox4 protein...