Reactive oxygen species derived from NADPH oxidase contribute to a wide variety of renal diseases. Nox4, the major NADPH isoform in kidney, produces mainly H₂O₂ that regulates physiological functions. Nox4 contributes to redox processes involved in diabetic nephropathy, acute kidney injury, obstructive nephropathy, hypertensive nephropathy, renal cell carcinoma and other renal diseases by activating multiple signaling pathways. Although Nox4 is found in a variety of cell types, including epithelial cells, podocytes, mesangial cells, endothelial cells and fibroblasts, its role is not clear and even controversial. In some conditions, Nox4 protects cells by promoting cell survival in response to harmful stimuli. In other scenarios it induces cell apoptosis, inflammation or fibrogenesis. This functional variability may be attributed to distinct cell types, subcellular localization, molecular concentrations, disease type or stage, and other factors yet unexplored. In this setting, we reviewed the function and mechanism of Nox4 in renal diseases, highlighted the contradictions in Nox4 literature, and discussed promising therapeutic strategies targeting Nox4 in the treatment of certain types of renal diseases.

源自NADPH氧化酶的活性氧会导致多种肾脏疾病。Nox4是肾脏中主要的NADPH亚型，主要产生H ₂ O ₂调节生理功能。Nox4通过激活多种信号通路，参与涉及糖尿病性肾病，急性肾损伤，阻塞性肾病，高血压肾病，肾细胞癌和其他肾脏疾病的氧化还原过程。尽管Nox4存在于多种细胞类型中，包括上皮细胞，足细胞，肾小球系膜细胞，内皮细胞和成纤维细胞，但其作用尚不明确，甚至存在争议。在某些情况下，Nox4通过促进细胞对有害刺激的存活来保护细胞。在其他情况下，它会诱导细胞凋亡，炎症或纤维化。这种功能变异性可归因于不同的细胞类型，亚细胞定位，分子浓度，疾病类型或阶段以及尚未探索的其他因素。在这种情况下，