Department of Pediatrics, The first affiliated hospital of Bengbu Medical College, Bengbu 233004, Anhui, China.
Department of radiation oncology, The first affiliated hospital of Bengbu Medical College, Bengbu 233004, Anhui, China.
Cell Mol Biol (Noisy-le-grand). 2023 Sep 30;69(9):201-206. doi: 10.14715/cmb/2023.69.9.31.
Asthma is a respiratory inflammatory disease, and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is involved in the progression of respiratory diseases. However, the role of NOX4 in asthma remains unclear. In the present study, we aimed to explore the effects of NOX4 on airway remodeling and inflammation. NOX4 expression was measured using immunocytochemistry (IHC), western blot, and real-time PCR (qPCR). Lung tissues were stained using the H&E assay. ELISA was used to examine the levels of airway remodeling-related indicators, and qPCR was used to detect airway inflammatory factors. The results indicated that NOX4 is highly expressed in lung tissues, bronchoalveolar lavage fluid (BALF), and serum of OVA-treated mice. Inhibition of NOX4 alleviated OVA-induced airway remodeling and inflammation. Similarly, TGF-β1 was also upregulated in BALF and serum OVA-induced mice. Inhibition of TGF-β1 signaling also improved airway remodeling and inflammation induced by OVA. Moreover, the downregulation of NOX4 inactivated the TGF-β1-Smad2/3 pathway, and TGF-β1 decreased Smad2/3 expression. Moreover, inhibition of the TGF-β1 was enhanced, while TGF-β1 reversed the effects on airway remodeling and inflammation induced by NOX4 inhibition. Taken together, the downregulation of NOX4 improves airway remodeling and inflammation via inactivation of the TGF-β1-Smad2/3 pathway in asthma mice, suggesting that NOX4 may be a therapeutic target for asthma.
哮喘是一种呼吸道炎症性疾病，烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4（NOX4）参与了呼吸道疾病的进展。然而，NOX4 在哮喘中的作用尚不清楚。在本研究中，我们旨在探讨 NOX4 对气道重塑和炎症的影响。使用免疫细胞化学（IHC）、western blot 和实时 PCR（qPCR）测量 NOX4 的表达。使用 H&E 染色法对肺组织进行染色。使用 ELISA 检测气道重塑相关指标的水平，使用 qPCR 检测气道炎症因子。结果表明，NOX4 在肺组织、支气管肺泡灌洗液（BALF）和 OVA 处理小鼠的血清中高表达。抑制 NOX4 可减轻 OVA 诱导的气道重塑和炎症。同样，TGF-β1 在 BALF 和血清 OVA 诱导的小鼠中也上调。抑制 TGF-β1 信号也改善了 OVA 诱导的气道重塑和炎症。此外，NOX4 的下调使 TGF-β1-Smad2/3 通路失活，TGF-β1 降低了 Smad2/3 的表达。此外，抑制 TGF-β1 增强，而 TGF-β1 逆转了 NOX4 抑制诱导的气道重塑和炎症的作用。总之，NOX4 的下调通过使哮喘小鼠中的 TGF-β1-Smad2/3 通路失活来改善气道重塑和炎症，这表明 NOX4 可能是哮喘的治疗靶点。
