Osthole Attenuates Bleomycin-Induced Pulmonary Fibrosis by Modulating NADPH Oxidase 4-Derived Oxidative Stress in Mice
Autor: | Wei Wang, Yujia Lu, Hongmei Gao, Pengqi Wang, Feng Xu, Anju Zuo, Ruijuan Lv, Linmao Lyu, Jiazheng Chen, Lijun Fang, Tao Yan, Yuguo Chen |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
Aging Article Subject Lung injury Bleomycin medicine.disease_cause Biochemistry Transforming Growth Factor beta1 Mice chemistry.chemical_compound Idiopathic pulmonary fibrosis Coumarins Pulmonary fibrosis medicine Animals Humans Smad3 Protein Myofibroblasts Lung Cell Proliferation Antibiotics Antineoplastic NADPH oxidase QH573-671 biology Chemistry urogenital system fungi NOX4 Cell Differentiation Cell Biology General Medicine respiratory system medicine.disease Idiopathic Pulmonary Fibrosis respiratory tract diseases Mice Inbred C57BL Survival Rate Disease Models Animal Oxidative Stress medicine.anatomical_structure NADPH Oxidase 4 Cancer research biology.protein Cytology Reactive Oxygen Species Oxidative stress Research Article |
Zdroj: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2021 (2021) |
ISSN: | 1942-0900 |
DOI: | 10.1155/2021/3309944 |
Popis: | Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the extensive accumulation of myofibroblasts and collagens. However, the exact mechanism that underlies this condition is unclear. Growing evidence suggests that NADPH oxidases (NOXs), especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin (BLM) is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole (OST) is an active constituent of the fruit of Cnidium ninidium. Here, we used an in vivo mouse model and found that OST suppressed BLM-induced body weight loss, lung injury, pulmonary index increase, fibroblast differentiation, and pulmonary fibrosis. OST also significantly downregulated BLM-induced NOX4 expression and oxidative stress in the lungs. In vitro, OST could inhibit TGF-β1-induced Smad3 phosphorylation, differentiation, proliferation, collagen synthesis, NOX4 expression, and ROS generation in human lung fibroblasts in a concentration-dependent manner. Moreover, NOX4 overexpression could prevent the above effects of OST. We came to the conclusion that OST could significantly attenuate BLM-induced pulmonary fibrosis in mice, via the mechanism that involved downregulating TGF-β1/NOX4-mediated oxidative stress in lung fibroblasts. |
Databáze: | OpenAIRE |
Externí odkaz: |