ライフサイエンスコーパス: NOX4

1 n species-generating enzyme NADPH oxidase 4 (Nox4).

2 ting from the activation of NADPH oxidase 4 (NOX4).

3 xpression through the NADPH oxidase isoform, NOX4.

4 .-) production or the expression of Nox1 and Nox4.

5 n primary cardiomyocytes with a knockdown of Nox4.

6 most enriched pathways that were altered by Nox4.

7 nd blocks high glucose induction of Nox2 and Nox4.

8 demonstrate posttranslational regulation of Nox4.

9 n-proteasomal system-mediated degradation of Nox4.

10 otal cell ROS and the NADPH oxidase isoform, Nox4.

11 dria act as an allosteric switch to activate NOX4.

12 ts with genetic deficiency (or silencing) of Nox4.

13 Co-IP) in HEK293 cells stably overexpressing NOX4.

14 ase, interacts with the C-terminal domain of NOX4.

15 adrenergic agonist, induced upregulation of Nox4 (1.5-fold; P<0.05) within 5 minutes, accompanied by

16 d in at least two rodents and humans, making NOX4 a prime target for a first-in-class mechanism-based

17 NADPH oxidase 4 (NOX4), a constitutively active enzymatic source of ROS,

18 onfirmed to directly target NADPH oxidase 4 (NOX4), a reactive oxygen species generator known to dama

19 NADPH oxidase 4 (NOX4), a source of cellular superoxide anions, has multi

20 NADPH oxidase4 (NOX4), a target of miR-25, was significantly increased i

21 NOX4, a potent reactive oxygen species generator, was co

22 Inhibition of Nox4 abolishes the increase in ROS and peroxynitrite gen

23 tricular fibroblasts to TGF-beta1, including Nox4 activation, implicating a crosstalk between nicotin

24 he development of cardiac arrhythmia, namely NOX4 activation, subsequent NOX4-specific NADPH-driven R

25 Furthermore, we show that elevated NOX4 activity accelerates oxidation of NADH and supports

26 eta signaling, TGF-beta release from bone or Nox4 activity improved muscle function in mice with MDA-

27 s study we explored the role of constitutive Nox4 activity in regulating mitochondrial function.

28 ATP directly binds and negatively regulates NOX4 activity.

29 ls may have application for monitoring renal NOX4 activity.

30 Whether Nox4 acts as a sensor of energy stress to mediate activa

31 Here we discover that NAD(P)H oxidase 4 (NOX4), an enzyme known to catalyse the oxidation of NAD(

32 We aimed to investigate the role of Nox4, an endothelial generator of H2O2, in the regulatio

33 Both NOX4 and CD44v6 are up-regulated in the lungs of mice su

34 oteins is required for the ubiquitination of Nox4 and for maintaining low basal levels of this reacti

35 inhibits high glucose-induced expression of NOX4 and matrix protein and whether H2S and NO pathways

36 d MC fibronectin accumulation and identifies Nox4 and mitochondrial ROS as mediators of eNOS dysfunct

37 delayed manner relative to the induction of Nox4 and myofibroblast differentiation.

38 mice with fulvene-5, a specific inhibitor of NOX4 and NADPH oxidase 2 (NOX2), decreased their elevate

39 HG also increases the levels of Nox4 and Nox1 and NADPH oxidase activity.

40 R by low-dose rapamycin decreases HG-induced Nox4 and Nox1, NADPH oxidase activity, and podocyte apop

41 We investigated the role of Nox4 and Nox4-associated signaling pathways in the devel

42 se results indicate a critical role for both Nox4 and Nrf2 in counter-regulation of mitochondrial bio

43 We also observed that NOX4 and p22(phox) localize to the nuclear membrane in M

44 or TGF-beta-induced upregulation of p-MeCP2, NOX4 and primary miR-25, but downregulation of precursor

45 d the ROS generation enzyme NADPH oxidase 4 (NOX4) and induced the activation of NF-E2-related factor

46 ical candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosamino

47 bited ROS generation enzyme NADPH oxidase 4 (NOX4), and increased dual specificity phosphatase 6 (DUS

48 assayed and NADPH oxidase isoforms, Nox2 and Nox4, and antioxidant enzymes were determined by immunob

49 d modified expression, including EDN1, APLN, NOX4, and CBS.

50 The intestinal epithelium expresses NOX1, NOX4, and DUOX2, whose functions are not well understood

51 Ps included those in the DNMT2, DPEP1, FUT2, NOX4, and PON1 genes.

52 ding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively re

53 NADPH oxidase (Nox) 2 and Nox4 are major components of the Nox family which purpos

54 mechanisms of transcriptional regulation of NOX4 are not well understood.

55 We investigated the role of Nox4 and Nox4-associated signaling pathways in the development of

56 milarly, skeletal muscle weakness, increased Nox4 binding to RyR1 and oxidation of RyR1 were present

57 er IGF-I stimulation and was responsible for Nox4 binding to the SH2 domain of Grb2.

58 development of therapeutic regimens aimed at NOX4 blockade.

59 Endothelial NOX4 breaks down the BBB, while neuronal NOX4 leads to n

60 Knockdown of Nox4, but not Nox2, attenuated O(2)(-) production in the

61 Selective knockdown of Nox4, but not Nox2, or selective reduction of ROS in the

62 The pharmacologic inhibition of NOX4 by either GKT137831, which is currently in phase 2

63 The Nox4 cardiac metabolome was then investigated by (1)H nu

64 FYN and NOX4 colocalized in perinuclear mitochondria, ER, and nu

65 Moreover, low expression of NOX4 combined with high expression of either RhoC or Cdc

66 Calnexin also resided in NOX4-containing complexes as demonstrated by complexome

67 Both Nox2 and Nox4 contribute to the increase in reactive oxidative sp

68 Nox4 critically mediates autophagy in response to energy

69 A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV mac

70 In contrast, NOX4 deficiency did not inhibit the activation of the NL

71 as the increase in mitochondrial proteins in Nox4-deficient lung fibroblasts is inhibited by silencin

72 tic TNF-alpha and PCNA responses subsided in Nox4-deficient mice compared with wildtype mice.

73 Furthermore, Nox4-deficient mice showed substantial reduction in casp

74 enuated in primary hepatocytes isolated from Nox4-deficient mice.

75 ses in human hepatoma cells and wildtype and Nox4-deficient mice.

76 of oxidative-related genes, such as Rac1 and Nox4 demonstrated by both in vivo and in vitro studies.

77 ese data provide a novel mechanistic link of Nox4-dependent activation of mTORC2 via the energy senso

78 creased during glucose deprivation (GD) in a Nox4-dependent manner.

79 However, the mechanisms by which NOX4-dependent metabolic regulation affect the innate im

80 MC fibronectin synthesis through blockade of Nox4-dependent ROS and peroxynitrite generation, with su

81 Moreover, the effect of Nox4 depletion was time-dependent; following six weeks o

82 IF-1alpha), downstream of NAD(P)H oxidase-4 (NOX4)-derived reactive oxygen species (ROS).

83 We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300

84 eam effector signaling pathways activated by Nox4-derived reactive oxygen species in the myocardium.

85 Nox4-derived reactive oxygen species production mediates

86 nsight into the mechanism by which localized Nox4-derived ROS regulates the sustained activity of a t

87 n vitro oxidation experiments indicated that Nox4-derived ROS was able to oxidize Src when they are i

88 We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epitheliu

89 We aimed to identify novel Nox4-driven cardioprotective mechanisms that promote ada

90 ecent studies have found that an increase in Nox4 during pressure overload protects the heart against

91 ric oxide synthase 2, NADPH oxidase (NOX) 2, NOX4, E-selectin, and monocyte chemotactic protein-1.

92 dependent protein kinase II was increased in NOX4 embryos but diminished by polyethylene glycol-conju

93 Intriguingly, NOX4 embryos developed cardiac arrhythmia that is charac

94 analyzed by an established LQ-1 program, the NOX4 embryos displayed much more variable beat-to-beat i

95 Both the phenotype and the increased ROS in NOX4 embryos were attenuated by NOX4 morpholino co-injec

96 at in control embryos versus 0.038 s/beat in NOX4 embryos).

97 Expression levels of Nox4-encoded mRNA and protein increased only in the diab

98 NADPH oxidase 4 (NOX4) enzyme, which catalyzes the reduction of O2 to hyd

99 ted with a significantly decreased number of NOX4+ epithelial cells in the intestines of THC-treated

100 Although necessary, MRTF is insufficient; Nox4 expression also requires TGFbeta-activated Smad3 an

101 High glucose increased NOX4 expression and activity at 24 h in renal proximal t

102 Hic-5 silencing induced constitutive Nox4 expression and enhanced TGF-beta1-inducible Nox4 le

103 I infusion to control mice increased cardiac Nox4 expression and induced fibrosis and hypertrophy.

104 Moreover, MRTF inhibition prevents Nox4 expression during TGFbeta-induced fibroblast-myofib

105 NOX4 expression in cardiomyocytes (CMs) plays an importa

106 itant normalization of GSH concentration and Nox4 expression in diabetic mice.

107 , and that ATM inhibition leads to increased NOX4 expression in normal cells.

108 er capture microdissection reveals increased Nox4 expression in the tubular epithelium also during ob

109 TAZ/YAP mitigates injury-induced epithelial Nox4 expression in vitro and in vivo.

110 In HCC patients, NOX4 expression inversely correlates with RhoC and Cdc42

111 Moreover, NOX4 expression is associated with E-cadherin levels and

112 We showed that NOX4 expression levels are higher in A-T cells, and that

113 NaHS inhibition of high glucose-induced NOX4 expression was abrogated by N(omega)-nitro-l-argini

114 , the increased TGF-beta1 responsiveness and Nox4 expression were documented in the atria of transgen

115 on via NADPH oxidase signaling, up-regulated Nox4 expression, and promoted NF-kappaB dependent promot

116 istration of 7-KC concomitantly up-regulated Nox4 expression, increased intracellular hydrogen peroxi

117 d cardiac remodeling and robust elevation in Nox4 expression, indicating that AngII worsens cardiac i

118 generate NO to inhibit high glucose-induced NOX4 expression, oxidative stress, and matrix protein ac

119 tive effects of NaHS on high glucose-induced NOX4 expression, reactive oxygen species generation, and

120 ted transcription factor, decreases Nox2 and Nox4 expression, whereas NFAT overexpression increases N

121 us cytoskeleton organization) could regulate Nox4 expression.

122 ardiac injury, at least in part by enhancing Nox4 expression.

123 eacetylation of NF-kappaB and suppression of NOX4 expression.

124 nto osteoclasts with RANKL and M-CSF induced Nox4 expression.

125 nted NaHS inhibition of high glucose-induced NOX4 expression.

126 ons led to reduced superoxide production and NOX4 expression.

127 Inhibition of Nox4 expression/activity by genetic or pharmacological a

128 H) concentration and higher NADPH oxidase 4 (Nox4) expression, consistent with increased superoxide g

129 High-glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species generation, an

130 Our results suggest that endogenous NOX4 forms macromolecular complexes with calnexin, which

131 s a novel redox signaling pathway, involving Nox4-GADD34 interaction and a targeted oxidative inactiv

132 Importantly, NOX4 gene deletions are frequent in HCC patients, correl

133 es insights into the molecular mechanisms of NOX4 gene expression, informing novel therapeutic approa

134 in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung flui

135 TGF-beta1-induced NOX4 gene promoter activation requires a region between

136 S site of the NOX4 promoter is essential for NOX4 gene transcription induced by TGF-beta1 in human lu

137 ranscriptional start site (TSS) of the human NOX4 gene were generated and their relative responsivene

138 NADPH oxidase 4 (Nox4) generates reactive oxygen species (ROS) that can m

139 nd reactive oxygen species (NADPH oxidase 4 (NOX4))-generating enzymes by classical activation pathwa

140 xpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association.

141 a expression in RCC cells, the NADPH oxidase NOX4 has been identified, but the pathogenic contributio

142 Nox4 has been implicated in the basal production of ROS

143 The NADPH oxidase (NOX) isoform NOX4 has been linked with diabetic kidney disease (DKD).

144 nduced in HSC by acetaldehyde treatment, and NOX4 has significantly increased mRNA half-life of CCR2

145 Inhibition of Nox4 has therapeutic potential to treat cardiac remodeli

146 NADPH oxidase 4 (Nox4) has been implicated in cardiac remodeling, but its

147 A preference for fatty acid oxidation in Nox4 hearts correlated with a better energetic state (ph

148 Cardiomyocyte-targeted Nox4 hearts preferentially oxidised fatty acids for ener

149 rtic arch endothelia exhibited elevated ROS, NOX4, HIF-1alpha, and glycolytic enzyme and PDK1 express

150 alpha, and IL-6 was significantly reduced in NOX4(HSCKO) compared to fl/fl mice.

151 c damage is due to an organ-specific role of NOX4 in blood-brain-barrier endothelial cells and neuron

152 Therefore, we studied the role of NOX4 in bone homeostasis.

153 d serves as a negative feedback regulator of NOX4 in CMs during cardiac remodeling.

154 approaches to interfere with upregulation of NOX4 in diseases characterized by activation of the TGF-

155 g miR-25 processing and thereby upregulating NOX4 in early diabetic nephropathy.

156 e examined the transcriptional regulation of NOX4 in human lung fibroblasts by TGF-beta1.

157 We investigated the role of Nox2 and Nox4 in mediating oxidative stress and myocardial injury

158 oper maturation, processing, and function of NOX4 in the endoplasmic reticulum.

159 Upregulation of Nox4 in the myocardium causes cardiac remodeling through

160 In this study we identified a novel role for Nox4 in the regulation of cardiac fatty acid oxidation.

161 Induction of Nox4 in vitro and in the podocyte-specific NOX4 transgen

162 e report that podocyte-specific induction of NOX4 in vivo was sufficient to recapitulate the characte

163 xidative stress and reduced NAPDH oxidase 4 (NOX4) in glomeruli of diabetic eNOS(-/-) mice.

164 rk, we examined the role of NADPH oxidase 4 (Nox4) in LPS-induced TLR4 responses in human hepatoma ce

165 ed up-regulation of NADPH oxidase isoform 4 (NOX4) in patients with atrial fibrillation, which is acc

166 dant enzymes, including Gpxs, Prdx, Sod, and Nox4, in mediating this effect.

167 Therefore, loss of NOX4 increases actomyosin levels and favours an epitheli

168 ereas NFAT overexpression increases Nox2 and Nox4, indicating that the CnAbeta/NFAT pathway modulates

169 2 at days 15 to 28 suppressed mTORC2 but not Nox4, induced smooth muscle-specific apoptosis in small

170 CMs, and FYN expression negatively regulated NOX4-induced O2- production and apoptosis in CMs.

171 and diabetic mice and was attenuated by NOX1/NOX4 inhibition in diabetic mice.

172 neuroprotective potential of pharmacological NOX4 inhibition was confirmed in an ex vivo model, free

173 uman tissue), and administration of the NOX1/NOX4 inhibitor increased glomerular FH levels in diabeti

174 Intervention with a NOX1/NOX4 inhibitor reduced albuminuria, glomerular hypertrop

175 ate levels were uniquely reduced by the NOX1/NOX4 inhibitor.

176 e glycol-conjugated superoxide dismutase, or NOX4 inhibitors fulvene-5, 6-dimethylamino-fulvene, and

177 Furthermore, the NADPH oxidase NOX4 inhibits this transition and therefore suppresses e

178 es are consequences of a so far unidentified NOX4-interacting protein.

179 The calnexin NOX4 interaction could be confirmed by reverse Co-IP and

180 In conclusion, NOX4 is a major mediator of diabetes-associated glomerul

181 We, therefore, conclude that Nox4 is a positive transcriptional regulator of CSE in e

182 ivation in PDAC development and suggest that NOX4 is a potential therapeutic target for PDAC.

183 Our results offer direct evidence that NOX4 is critical for renal tumorigenesis and they show h

184 beta-induced expression of the NADPH oxidase Nox4 is essential for fibroblast-myofibroblast transitio

185 In conclusion, NOX4 is induced in early alcoholic liver injury and regu

186 We investigated whether Nox4 is involved in the regulation of autophagy and cell

187 NOX4 is necessary to maintain parenchymal structures, in

188 Within the family of NADPH oxidases, NOX4 is unique as it is predominantly localized in the e

189 oupling triggered by Ang II, indicating that Nox4 is upstream of eNOS.

190 NADPH oxidase 4 (NOX4) is a member of the NADPH oxidase gene family that

191 e oxygen species-generating NADPH oxidase-4 (Nox4) is induced downstream of ATF4, binds to a PP1-targ

192 ge, the first evidence that NADPH oxidase 4 (NOX4) is involved in manifesting A-T disease.

193 and up-regulation of mRNA level of NOX 2 and NOX4 isoforms in neuronal cells.

194 Nox4 knockdown abrogates epithelial-myofibroblast transi

195 n cell survival during GD in the presence of Nox4 knockdown was rescued by reactivation of autophagy

196 verexpression to remove hydrogen peroxide or Nox4 knockdown with siRNA reduced intracellular hydrogen

197 for 14 days, wild-type and cardiac-specific Nox4 knockout mice exhibited similar aortic pressures.

198 We generated HSC-specific NOX4 KO mice and these were pair-fed on alcohol diet.

199 out (KO), sNox4 KO, and cardiac-specific (c) Nox4 KO mice were subjected to I/R (30 minutes/24 hours,

200 that only in the brain does NADPH oxidase 4 (NOX4) lead to ischemic damage.

201 ial NOX4 breaks down the BBB, while neuronal NOX4 leads to neuronal autotoxicity.

202 Nox4 levels and mTORC2 signaling were significantly upre

203 erebelli from A-T patients revealed elevated NOX4 levels.

204 expression and enhanced TGF-beta1-inducible Nox4 levels.

205 We find that NOX4 localizes to the inner mitochondria membrane and th

206 ude that, in A-T disease in humans and mice, NOX4 may be critical mediator and targeting it will open

207 iabetic nephropathy and CKD; upregulation of Nox4 may be important in renal oxidative stress and kidn

208 We found that Nox4 mediated LPS-TLR4 signaling in hepatocytes via NF-k

209 Our results suggest that NOX4-mediated FAO promotes NLRP3 inflammasome activation

210 er injury has not been addressed, we studied NOX4-mediated regulation of CCR2/CCL2 mRNA stability.

211 Therefore, our data suggest that Nox4 mediates LPS-TLR4 signaling in human hepatoma cells

212 dertaken to determine the mechanism by which Nox4 mediates sustained Src activation.

213 Nox4(-/-) mice displayed higher bone density and reduced

214 eased ROS in NOX4 embryos were attenuated by NOX4 morpholino co-injection, treatments of the embryos

215 es with TGFbeta to facilitate MRTF-dependent Nox4 mRNA expression/promoter activation.

216 (TGF-beta1) is known to induce expression of NOX4 mRNA in mesenchymal cells.

217 NOX4 mRNA was significantly induced in patients with alc

218 Overexpression of a Nox4 mutant, Y491F, prevented Nox4/Grb2 association.

219 ted a potential role for Hic-5 in regulating Nox4, myofibroblast differentiation, and senescence.

220 ting mitochondrial ROS generation attenuated NOX4 (NADPH oxidase 4) expression, which is required for

221 gII-infused c-hNox4Tg mice with GKT137831, a Nox4/Nox1 inhibitor, abolished the increase in oxidative

222 equences of five NOX genes (nox1, nox2/cybb, nox4, nox5, and duox) have been identified in the zebraf

223 The ROS-dependent activation, mediated by Nox4, of widely expressed redox-regulated transcription

224 verexpression, indicating that the effect of Nox4 on cell survival is critically mediated through reg

225 NADPH oxidase 2 (Nox2) inhibition, but not Nox4 or Nox1 inhibition, attenuated LPS-induced superoxi

226 Nox2 silencing, but not Nox4 or Nox1 silencing, inhibited LPS-mediated inhibitor

227 arison of heart tissue from cardiac-targeted Nox4-overexpressing mice and controls.

228 gated the impact on the cardiac phenotype of NOX4 overexpression in zebrafish.

229 Cardiac-targeted Nox4 overexpression profoundly remodelled the cardiac pr

230 Injection of NOX4-P437H mutant RNA had no effect on the cardiac pheno

231 characterized by activation of the TGF-beta1/NOX4 pathway.

232 Nox4 plays an essential role in mediating cysteine oxida

233 Nox4 promoted autophagy during GD through activation of

234 instead, it triggered p38- and MK2-mediated, Nox4-promoted MRTF phosphorylation and activation.

235 n-provoked Nox4 protein and mRNA expression, Nox4 promoter activation, and reactive oxygen species pr

236 1 inducibility to the non-responsive -3.97kb NOX4 promoter construct.

237 Because the Nox4 promoter harbors a serum response factor/MRTF cis-e

238 b and 4.76kb upstream of the TSS site of the NOX4 promoter is essential for NOX4 gene transcription i

239 NOX4 promoter was induced in HSC by acetaldehyde treatme

240 ated TGF-beta1 responsiveness of the -4.76kb NOX4 promoter.

241 eliminates the synergistic activation of the Nox4 promoter.

242 ppresses TGFbeta/contact disruption-provoked Nox4 protein and mRNA expression, Nox4 promoter activati

243 hibited an approximately 10-fold increase in Nox4 protein expression and an 8-fold increase in the pr

244 in cellular and mitochondrial ROS as well as Nox4 protein expression and NADPH oxidase activation, wh

245 on, and urinary albumin excretion as well as NOX4 protein expression and NADPH-dependent reactive oxy

246 response to calnexin shRNA reduced cellular NOX4 protein expression and reactive oxygen species form

247 ivities of myofibroblasts by down-regulating Nox4 protein expression.

248 The induction of constitutive Nox4 protein in Hic-5-silenced cells was independent of

249 We show that Nox4 protein is robustly induced in kidney tubular cells

250 Ang II rapidly up-regulates Nox4 protein.

251 NADPH oxidase 4 (Nox4) protein levels were increased in idiopathic PAH PA

252 how TGF-beta-1-induced CD44V6 regulates the NOX4/reactive oxygen species (ROS) signaling that mediat

253 Importantly, it also prevented Nox4 recruitment to SHPS-1.

254 Cells expressing this mutant had impaired Nox4 recruitment to SHPS-1.

255 Therefore we hypothesized that Nox4 recruitment to the plasma membrane scaffold SHPS-1

256 To determine the mechanism of Nox4 recruitment, we analyzed the role of Grb2, a compon

257 oxidative species produced by either Nox2 or Nox4 regulate hypoxia-inducible factor-1alpha and peroxi

258 We show that this Nox4-regulated pathway robustly enhances cell survival a

259 species-generating enzyme, NADPH oxidase 4 (Nox4), regulates a number of physiological and pathologi

260 Rho has been implicated in Nox4 regulation, but the underlying mechanisms are large

261 c understanding of the downstream effects of NOX4 remains to be established.

262 Activation of NOX4 requires catalytic subunit p22(phox), which is upre

263 Deletion of Nox4 rescued the exaggerated LV remodeling in FYN-defici

264 Here we show that deficiency of NOX4 resulted in reduced expression of carnitine palmito

265 ne destruction, upregulated NADPH oxidase 4 (Nox4), resulting in elevated oxidization of skeletal mus

266 One-cell stage embryos were injected with NOX4 RNA prior to video recording of a GFP-labeled (myl7

267 a1/TGFbetaRI signaling that acts to increase NOX4/ROS production, which is required for myofibroblast

268 Specifically, we found that NOX4/ROS regulates hyaluronan synthesis and the transcri

269 Here, we report that NOX4 silencing in VHL-deficient RCC cells abrogates cell

270 Notably, NOX4 silencing or superoxide scavenging was sufficient t

271 Nox4 silencing suppressed LPS-induced TNF-alpha and PCNA

272 Finally, we show that NOX4 silencing, through PKM2, sensitizes cultured and ex

273 rhythmia, namely NOX4 activation, subsequent NOX4-specific NADPH-driven ROS production, and redox-sen

274 hat observed in mesenchymal cell types, here NOX4 suppresses Rho and Cdc42 GTPase expression and down

275 al for renal tumorigenesis and they show how NOX4 suppression and VHL re-expression in VHL-deficient

276 /PKCzeta) and their disruption of attenuated Nox4 synthesis (76 +/- 9% reduction).

277 osphorylated p65 rel, which led to increased Nox4 synthesis.

278 at hyperglycemia stimulated NADPH oxidase 4 (Nox4) synthesis, and IGF-I facilitated its recruitment t

279 Vascular smooth muscle NOX4, the common denominator of ischemia within all isch

280 We found that LPS increased expression of Nox4, TNF-alpha, and proliferating cell nuclear antigen

281 uman endothelial cells in vitro demonstrated Nox4 to be a positive regulator of CSE transcription and

282 We demonstrate here the potential of Nox4 to drive cardiomyocyte differentiation in pluripote

283 he isoform-specific contribution of Nox2 and Nox4 to ischemia/reperfusion (I/R) injury is poorly unde

284 However, whether CD44V6 regulates NOX4 to mediate tissue repair and fibrogenesis is not we

285 ntified, but the pathogenic contributions of NOX4 to RCC have not been evaluated directly.

286 lectrophorese combined with SDS-PAGE yielded NOX4 to reside in macromolecular complexes.

287 sphate 5-kinase 1alpha, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving intern

288 Cardiac-specific human Nox4 transgenic mice (c-hNox4Tg) were generated.

289 lpha and TGF-beta expression was observed in NOX4 transgenic mice and diabetic mice and was attenuate

290 phy we demonstrate that endothelial-specific Nox4 transgenic mice exhibit a hypo-contractile phenotyp

291 al cells, isolated from endothelial-specific Nox4 transgenic mice, compared with wild-type littermate

292 f Nox4 in vitro and in the podocyte-specific NOX4 transgenic mouse led to reduced FH levels.

293 We determined that Nox4 Tyr-491 was phosphorylated after IGF-I stimulation

294 rial reactive oxygen species production, and Nox4 upregulation.

295 Knockdown of NOX2 and NOX4, using specific siRNA, reduced both basal and S1P-i

296 at direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulat

297 Mechanistically, NOX4 was induced through p16-Rb-regulated E2F and p22(ph

298 Protein levels of p-MeCP2, HIPK2, and NOX4 were increased in high glucose (HG)- or TGF-beta-tr

299 ein levels and the ROS-producing activity of Nox4 were increased in the endoplasmic reticulum (ER), b

300 re partially abrogated by down-regulation of NOX4 with siRNA.

301 actions were also significantly impaired in Nox4 Y491F-overexpressing cells.