NADPH oxidase 4 (NOX4) (NOX4)

NADPH oxidase 4 (NOX4) is a transmembrane enzyme that belongs to the NOX family of NADPH oxidases, primarily responsible for the constitutive generation of reactive oxygen species (ROS), specifically hydrogen peroxide (H2O2) [UniProt: Q9NPH5]. Unlike other family members, NOX4 activity is largely regulated by its expression levels rather than by cytosolic subunits, making it a key mediator in the gene expression/oxidative stress pathway [PubMed: 28611154]. It plays a critical role in cellular signaling, particularly in response to transforming growth factor-beta (TGF-beta), which drives myofibroblast activation and extracellular matrix deposition [PubMed: 31405806]. Pathologically, NOX4 is upregulated in various fibrotic conditions, including idiopathic pulmonary fibrosis, diabetic nephropathy, and liver cirrhosis, where excessive ROS production leads to tissue damage and organ dysfunction [PubMed: 22319113]. Therapeutic targeting of NOX4 involves small-molecule inhibitors like Setanaxib (GKT137831), which aim to reduce oxidative stress and halt the progression of chronic inflammatory and fibrotic diseases [ClinicalTrials.gov: NCT05011305].

Other names

Renal NADPH oxidaseRENOXKidney oxidase-1KOXKOX-1

Inhibition of NADPH oxidase enzymatic activity to reduce the constitutive production of reactive oxygen species, specifically hydrogen peroxide, thereby attenuating downstream oxidative stress-mediated gene expression and fibrotic signaling pathways [PubMed: 28611154].