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作者

Lijun Fang, Wei Wang, Jiazheng Chen, Anju Zuo, Hongmei Gao, Tao Yan, Pengqi Wang, Yujia Lu, Ruijuan Lv, Feng Xu, Yuguo Chen, Linmao Lyu

作者单位

Affiliations ¹ Department of Traditional Chinese Medicine, Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. ² School of Public Health, Shandong University, Jinan, China. ³ Department of Joint Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. ⁴ Department of General Medicine, Qilu Hospital of Shandong University, Jinan, China. ⁵ Department of Cardiology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China. ⁶ Department of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. ⁷ Cheeloo College of Medicine, Shandong University, Jinan, China. ⁸ Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China. ⁹ Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China. ¹⁰ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China. ¹¹ The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences: The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.

刊名

Oxidative medicine and cellular longevity

年份

2021

卷号

Vol.2021

页码

3309944

ISSN

1942-0994

摘要

Idiopathic pulmonary fibrosis 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 , especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole is an active co...更多

Idiopathic pulmonary fibrosis 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 , especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole 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.收起

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