The protective role of Nrf2 in the development of acute lung injury and pulmonary fibrosis

Nrf2在急性肺损伤和肺纤维化发展中的保护作用

• 批准号: 18590836
• 负责人: ISHII Yukio
• 金额: $ 2.55万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590836/
• 关键词: Transcription factors; Nrf2; Acute lung injury; Pulmonary fibrosis; Oxidative stress; Macrophages; Nrf2; マクロファージ; 急性肺傷害; 炎症

Oxidative stress may play an important role in the pthogenesis of acute lung injury and pulmonary fibrosis. Transcription factor Nrf2 counteracts oxidative tissue damage and inflammation through transcriptional activation via the antioxidant responsive element (ARE). To clarify the protective role of Nrf2 in the development of acute lung injury and pulmonary fibrosis, bleomycin was administrated to both C57BL/6 wild-type (WT) mice and Nrf2-knockout (Nrf2-/-) mice of the same background. The survival rate after bleomycin treatment was significantly decreased in Nrf2-/-mice compared with WT mice. The degree of acute lung injury, indicated by albumin concentration and the number of neutrophils in bronchoalveolar fluids, was much higher in Nrf2-/-mice than in WT mice 1 and 3 days after bleomycin administration. The degree of pulmonary fibrosis was also much greater in Nrf2-/-mice than in WT mice 28 days after bleomycin administration. The expression of antioxidant and phase 2 enzymes was inducible in the lungs of WT mice, but not in that of Nrf2-/- mice after bleomycin administration. Results indicated that Nrf2 protects against the development of acute lung injury and pulmonary fibrosis by lowering oxidative stress through regulating the expression of antioxidant molecules.

氧化应激可能在急性肺损伤和肺纤维化的发病过程中起重要作用。转录因子Nrf2通过抗氧化反应元件（ARE）的转录激活来抵消氧化组织损伤和炎症。为了阐明Nrf2在急性肺损伤和肺纤维化发生中的保护作用，我们在相同背景下对C57BL/6野生型（WT）小鼠和Nrf2敲除（Nrf2-/-）小鼠给予博来霉素。与WT小鼠相比，Nrf2-/-小鼠博来霉素治疗后存活率显著降低。在给予博来霉素1和3天后，Nrf2-/-小鼠的急性肺损伤程度（以支气管肺泡液白蛋白浓度和中性粒细胞数量为指标）明显高于WT小鼠。给予博来霉素28天后，Nrf2-/-小鼠的肺纤维化程度也比WT小鼠大得多。博莱霉素可诱导WT小鼠肺组织中抗氧化酶和2相酶的表达，但不能诱导Nrf2-/-小鼠肺组织中抗氧化酶和2相酶的表达。结果表明，Nrf2通过调节抗氧化分子的表达，降低氧化应激，对急性肺损伤和肺纤维化的发生具有保护作用。

项目成果

The role of transcription factor Nrf2 in the development of acute lung injury and pulmonary fidrosis

转录因子Nrf2在急性肺损伤和肺纤维化发生中的作用

• 发表时间: 2007
• 作者: Kikuchi N;lshii Y;et. al.
• 通讯作者: et. al.

Overexpression of GATA-3 protects against the development of hypersensitivity pneumoni

GATA-3 过度表达可预防过敏性肺炎的发生

• 发表时间: 2007
• 期刊: American Journal of Respiratory and Critical Care Medicine 176
• 作者: Matsuno Y;Ishii Y;et. al.
• 通讯作者: et. al.

転写因子Nrf2によるブレオマイ、シン誘発肺傷害および肺線維症の制御

转录因子 Nrf2 对博莱霉素、syn 诱导的肺损伤和肺纤维化的调节

• 发表时间: 2007
• 作者: 菊池教大・石井幸雄;他
• 通讯作者: 他

転写因子Nrf2によるブレオマイシン誘発肺傷害および肺線維症の制御

转录因子 Nrf2 对博来霉素诱导的肺损伤和肺纤维化的调节

• 发表时间: 2007
• 作者: 菊池教大;戸井幸雄;他
• 通讯作者: 他

Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis.

• DOI: 10.1164/rccm.200612-1887oc
• 发表时间: 2007-11
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: Y. Matsuno;Yukio Ishii;K. Yoh;Y. Morishima;N. Haraguchi;N. Kikuchi;T. Iizuka;T. Kiwamoto;S. Homma;A. Nomura;T. Sakamoto;M. Ohtsuka;N. Hizawa;Satoru Takahashi