Ang-(1-7)/Mas axis ameliorates bleomycin-induced pulmonary fibrosis in mice via restoration of Nox4-Nrf2 redox homeostasis

作者全名："Sheng, Min; Li, Qinke; Huang, Wenhan; Yu, Dan; Pan, Hang; Qian, Kechen; Ren, Feifeng; Luo, Lei; Tang, Lin"

作者地址："[Sheng, Min; Huang, Wenhan; Yu, Dan; Pan, Hang; Qian, Kechen; Ren, Feifeng; Luo, Lei; Tang, Lin] Chongqing Med Univ, Dept Rheumatol & Immunol, Affiliated Hosp 2, Chongqing, Peoples R China; [Li, Qinke] Chongqing Med Univ, Dept Urol, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："Tang, L (通讯作者)，Chongqing Med Univ, Dept Rheumatol & Immunol, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001134978400001

JCR分区：Q1

影响因子：5

年份：2024

卷号：962

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Pulmonary fibrosis; Ang-(1-7)/Mas axis; Fibroblast; Nox4-Nrf2 redox homeostasis

摘要："Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease characterized by diffuse alveolar inflammation, fibroblast differentiation, and the excessive deposition of extracellular matrix. During the pro -gression of PF, redox imbalance caused by excessive reactive oxygen species (ROS) production can result in further destruction of lung tissue. At present, data on the role of NADPH oxidase-4 (Nox4)-nuclear factor erythroid 2-related factor 2 (Nrf2) redox imbalance in PF are limited. The angiotensin (1-7) [Ang-(1-7)]/Mas axis is a protective axis in the renin-angiotensin system (RAS) that exerts antifibrotic effects. Therefore, this study aimed to investigate the role of the Ang-(1-7)/Mas axis in PF and to explore its mechanism in depth. The results revealed that the Ang-(1-7)/Mas axis inhibited TGF-beta 1-induced lung fibroblast differentiation, inflammation and fibrosis in bleomycin (BLM)-treated lung tissue. A mechanistic study suggested that the Ang-(1-7)/Mas axis may restore Nox4-Nrf2 redox homeostasis by upregulating the level of p62, reducing oxidative stress and the in-flammatory response and thus delaying the progression of lung fibrosis. This study provides a theoretical basis for exploring the mechanisms of PF and therapeutic targets for PF."

基金机构："National Natural Science Founda- tion of China [81771738]; Chongqing Science and Technology Innova- tion Leading Talent Support Program [CQYC202104]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0197]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [13-002-017]"

基金资助正文："This research was funded by the National Natural Science Founda- tion of China (81771738) , Chongqing Science and Technology Innova- tion Leading Talent Support Program (CQYC202104) , the Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0197) and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (13-002-017) ."